A multifunctional cobalt-organic framework for proton conduction and selective sensing of Fe3+ ions.

Developing multifunctional metal-organic frameworks (MOFs) is a new research trend. MOFs have shown remarkable performances in both proton conduction and fluorescence sensing, but the MOFs integrating the two performances are scarce. Herein, a Co-MOF, [Co6(oba)4(Hatz)(atz)(H2O)2(µ3-OH)2(µ2-OH)]·H2O (1, H2oba = 4,4-oxybis(benzoic acid), Hatz = 5-amino-1H tetrazole), has been assembled by Co2+ ions with H2oba and Hatz ligands, providing a unique example of multifunctional MOFs with both proton conduction and fluorescence sensing performances. The framework of 1 displays a pillar-layer structure built by the oba ligand as a pillar and a layer composed of Co-clusters and atz linkers. Because large-scale single crystals of 1 were successfully synthesized, the proton conduction ability of 1 was investigated using single crystal samples. 1 exhibits highly anisotropic conduction with conductivity values of 1.1 × 10-3 S cm-1 along the [001] direction and 9.1 × 10-6 S cm-1 along the [010] direction at 55 °C and 95% RH, respectively. Meanwhile, the fluorescence sensing of 1 towards metal ions was studied in aqueous solutions. Attractively, 1 may sensitively and selectively detect Fe3+ ions in the presence of other interfering ions by fluorescence quenching.

Successful treatment of a patient with an extraordinarily large deep burn.

BACKGROUND: Treatment of extraordinarily large deep burns remains a huge clinical challenge. CASE REPORT: This article is a summary of our experience with the treatment of a patient with an extraordinarily large deep burn (99.5% TBSA and 23% fourth degree burn) by using the "microskin autografting and alloskin repeated grafting" method to close the deep burn wound because of scarcity of skin sources of the patient. CONCLUSIONS: The patient has been observed for 2 years, and is able to face the reality of life peacefully with the support of his family.

Prevention and treatment of gastrointestinal dysfunction following severe burns: a summary of recent 30-year clinical experience.

AIM: To sum up the recent 30-year experience in the prevention and treatment of gastrointestinal dysfunction in severe burn patients, and propose practicable guidelines for the prevention and treatment of gastrointestinal (GI) dysfunction. METHODS: From 1980 to 2007, a total of 219 patients with large area and extraordinarily large area burns (LAB) were admitted, who were classified into three stages according the therapeutic protocols used at the time: Stage 1 from 1980 to 1989, stage 2 from 1990 to 1995, and stage 3 from 1996 to 2007. The occurrence and mortality of GI dysfunction in patients of the three stages were calculated and the main causes were analyzed. RESULTS: The occurrence of stress ulcer in patients with LAB was 8.6% in stage 1, which was significantly lower than that in stage 1 (P < 0.05). No massive hemorrhage from severe stress ulcer and enterogenic infections occurred in stages 2 and 3. The occurrence of abdominal distension and stress ulcer and the mortality in stage 3 patients with extraordinarily LAB was 7.1%, 21.4% and 28.5%, respectively, which were significantly lower than those in stage 1 patients (P < 0.05 or P < 0.01), and the occurrence of stress ulcer was also significantly lower than that in stage 2 patients (P < 0.05). CONCLUSION: Comprehensive fluid resuscitation, early excision of necrotic tissue, staged food ingestion, and administration of specific nutrients are essential strategies for preventing gastrointestinal complications and lowering mortality in severely burned patients.

Tissue injury by hot fluid containing nitrogen mustard.

Nitrogen mustards are analogous to sulfur mustard and have similar toxic effects on tissues. With the recent surge in terror activity, mustard could be used by terrorists. Recently a group of patients suffered from skin injury caused by hot fluid containing nitrogen mustard were treated. All the patients displayed eye symptoms such as eye pain, photophobia, excessive tearing, and blurred vision. One patient suffered from severe inhalation injury. Laboratory examination showed the decrease of white blood cell count, which may result from the loss of neutrophils. At the same time, platelets were at lower level during the first 8 days and gamma-glutamyltransferase (gamma-GT), a marker of oxidative stress, was significantly increased.

[Reconstruction and transplantation of the composite skin comprising epithelial growth factor gene-transfected keratinocytes].

OBJECTIVE: To investigate the epithelial growth factor (EGF) expression of EGF gene-transfected keratinocytes and its effect on cell proliferation after grafting. METHODS: Newborn Balb/c mouse keratinocytes and gene transfected keratinocytes were seeded on the surface of acellular dermal matrix and cocultured in different ratios as follows: 1:1, 1:3, or 1:5 1 week after culture. The composite skin was grafted onto the full-thickness wound in Balb/c mouse. Specimen was harvested at interval after grafting and underwent the immunohistochemistry staining for EGF and proliferating cell nuclear antigen (PCNA). RESULTS: Immunohistochemical staining showed EGF was expressed in the newly generated epidermis 1-2 week after grafting of the composite skin comprising Balb/c mouse keratinocytes and gene-transfected keratinocytes (at the ratio of 1:5). One week after surgery, Anti-PCNA positive basal cells were more than that in composite skin containing Balb/c mouse keratinocytes alone (P<0.01). CONCLUSION: The gene-transfected keratinocytes expresses EGF and promotes the proliferation of keratinocytes in the early stage after transplantation.

Overexpression of Hypo-Phosphorylated IκBß at Ser313 Protects the Heart against Sepsis.

IκBßis an inhibitor of nuclear factor kappa B(NF-κB) and participates in the cardiac response to sepsis. However, the role of the hypo-phosphorylated form of IκBß at Ser313, which can be detected during sepsis, is unknown. Here, we examined the effects of IκBß with a mutation at Ser313→Ala313 on cardiac damage induced by sepsis. Transgenic (Tg) mice were generated to overexpress IκBß, in which Ser-313 is replaced with alanine ubiquitously, in order to mimic the hypo-phosphorylated form of IκBß. Survival analysis showed that Tg mice exhibited decreased inflammatory cytokine levels and decreased rates of mortality in comparison to wild type (WT) mice, after sepsis in a cecal-ligation and puncture model (CLP). Compared to WT septic mice, sepsis in Tg mice resulted in improved cardiac functions, lower levels of troponin I and decreased rates of cardiomyocyte apoptosis, compared to WT mice. The increased formation of autophagicvacuoles detected with electron microscopy demonstrated the enhancement of cardiac autophagy. This phenomenon was further confirmed by the differential expression of genes related to autophagy, such as LC3, Atg5, Beclin-1, and p62. The increased expression of Cathepsin L(Ctsl), a specific marker for mitochondrial stress response, may be associated with the beneficial effects of the hypo-phosphorylated form of IκBß. Our observations suggest that the hypo-phosphorylated form of IκBß at Ser313 is beneficial to the heart in sepsis through inhibition of apoptosisand enhancement of autophagy in mutated IκBß transgenic mice.

Role of p38 mitogen-activated protein kinase in lung injury after burn trauma.

This study was undertaken to evaluate the effect of SB203580, a specific p38 mitogen-activated protein (MAP) kinase inhibitor, on burn-induced lung injury as well as the release of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta in rats to characterize the role of p38 MAP kinase in lung injury after burn trauma. Sprague-Dawley rats were divided into three groups: 1) sham group, or rats who underwent sham burn; 2) control group, or rats given third-degree burns over 30% total body surface area (TBSA) and lactated Ringer solution for resuscitation; and 3) SB203580 group, or rats given burn injury and lactated Ringers solution with SB203580 inside for resuscitation. Pulmonary injury was assessed at 24 h by pulmonary capillary permeability determined with fluorescein isothiocyanate-labeled albumin and lung histologic analysis. TNF-alpha and IL-1beta protein in bronchoalveolar lavage fluid and serum were measured by enzyme-linked immunosorbent assay and p38 MAP kinase was activity determined in lung by Western blot analysis. These studies showed that significant activation of p38 MAP kinase at 24 h postburn compared with control. Burn trauma resulted in increased pulmonary capillary leakage permeability, elevated levels of TNF-alpha and IL-1beta in bronchoalveolar lavage fluid and serum, and worsened histologic condition. SB203580 inhibited the activation of p38 MAP kinase, reduced the levels of TNF-alpha and IL-1beta, and prevented burn-mediated lung injury. These data suggest that p38 MAP kinase activation is one important aspect of the signaling event that may mediate the release of TNF-alpha and IL-1beta and contributes to burn-induced lung injury.

Role of p38 mitogen-activated protein kinase in Kupffer cell secretion of the proinflammatory cytokines after burn trauma.

This study was designed to investigate the role of p38 mitogen-activated protein (MAP) kinase on Kupffer cells (KCs) secretion of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta and hepatic injury following burn trauma. Sprague-Dawley rats were randomized into four groups: (1) sham burn rats given vehicle, (2) sham burn rats given the p38 MAP kinase inhibitor SB203580 (10mg/kg i.v., 15min and 12h after sham burn), (3) rats given a 30% total body surface area (TBSA) full-thickness burn and fluid resuscitation plus vehicle, and (4) burn rats given injury and fluid resuscitation plus SB203580. Rats from each group were killed at 24h post-burn to examine plasma aspartate transaminase (AST) and alanine transaminase (ALT) and KCs were isolated. The KCs secretion of TNF-alpha and IL-1beta and p38 MAP kinase activity (by Western blot analysis) were also examined. These studies showed by more significant activation of p38 MAP kinase in KCs harvested from burn rats than from shams. Burn trauma resulted in hepatic dysfunction and promoted KCs secretion of TNF-alpha and IL-1beta. SB203580 inhibited p38 MAP kinase activity, reduced KCs secretion of proinflammatory cytokines, and alleviated burn-mediated hepatic dysfunction. These data suggest p38 MAP kinase activation is one important aspect of the signaling event that may mediate the KCs secretion of proinflammatory cytokines TNF-alpha and IL-1beta following burn trauma.

Aggregation of the Intracellular Domain of the Human Thrombopoietin Receptor c-MPL.

Thrombopoietin (TPO) is the major cytokine which is involved in platelet production and exerts its effects via the receptor c-MPL. The yeast two-hybrid system has been used to study the aggregation of the intracellular domain of c-MPL in TPO signal transduction. First, the cDNA fragment of MPLP intracellular domain was amplified and cloned by using RT-PCR method from the total RNA of HEL cells. Then the cDNA fragment was sequenced and subcloned into two-hybrid vectors pAS2 and pGAD424, respectively, and the recombinants are named as pASMM and pGADMM. Co-transformation of these plasmids into yeast activated his3 and lacZ reporter genes, demonstrating in vivo interaction of the MPLP receptor intracellular domain itself. The aggregation may be important in TPO signal transduction.

[Role of p38 mitogen-activated protein kinase signal transduction pathway in the acute lung injury of severely burned rats].

OBJECTIVE: To investigate the role of p38 mitogen-activated protein kinase (MAPK) signal transduction pathway in the acute lung injury of severely burned rats. METHODS: Forty-eight adult healthy rats were randomly divided into three groups: sham group, burn control group, and burn + SB203580 group. A third-degree burns over 30% total body surface area rat model was used and pulmonary capillary permeability, lung water content, pulmonary histology and p38 MAPK activity were measured at 24 hours postburn. RESULTS: Burn trauma resulted in increased pulmonary capillary leakage permeability (42.5 +/- 4.7 vs. 12.1 +/- 1.4, P < 0.01), elevated lung water content (P < 0.05), and worsen histologic condition. There was a significant activation of p38 MAPK at 24 hours postburn compared with control. SB203580 inhibited the activation of p38 MAPK, reduced the pulmonary capillary leakage permeability (24.7 +/- 2.9 vs. 42.5 +/- 4.7, P < 0.01), decreased lung water content, and prevented burn-mediated lung injury. CONCLUSION: The activation of p38 MAPK is one important aspect of the signaling event that contributes to burn-induced lung injury.

Reduction of CD47 on monocytes correlates with MODS in burn patients.

Alternation of surface markers on monocytes is associated with the development of inflammation. The goals of the present study were to detect CD47 expression on monocytes by flow cytometry and explore its relationship with disease severity and MODS in burned patients. The results show CD47 expression on monocytes from all burned patients (n = 21) was lower than that from the healthy population (n = 21) for 24 days after burn. There was a significant difference in CD47 expression on monocytes between the patients with differing burn severity in the first 7 days after injury (P < 0.05). Considering the relationship between CD47 expression and MODS, we found the CD47 expression on monocytes from patients with MODS was lower (P < 0.05) in the first 3 days after injury than that from patients without MODS. In conclusion, diminished CD47 expression on monocytes is associated with burn severity and the occurrence of MODS in burn patients.

Risk factors and prognosis of lower digestive tract haemorrhage in severe burns: a 12-year retrospective analysis.

OBJECTIVE: To explore the risk factors relating to lower digestive tract haemorrhage in severe burns and summarise the experience in clinical diagnosis and treatment. METHOD: General data of 103 patients with severe extensive burns (EBs) admitted to our burn centre in Shanghai between 1997 and 2009 were reviewed retrospectively. The risk factors relating to EB-complicated lower digestive tract haemorrhage were analysed systematically with respect to the clinical features and experiences in treatment, and prognosis. RESULTS: Of the 103 severe EBs, five developed lower digestive tract haemorrhage with an occurrence of 4.9%. Four of them were proved to have multiple mucosal erosions in caecum, colon and rectum, and the remaining one was proved rectal ulcerative haemorrhage. In comparison with upper digestive tract haemorrhage, lower digestive tract haemorrhage in the present group was characterised by a longer duration (median 4.0 days, interquartile range (IQR) 1.5-14.5 days vs. median 2.0 days (IQR 1.0-3.0 days), P < 0.05). Deep burns, especially fourth-degree burns, with complications of severe systemic infection, formed the main risk factors relating to lower digestive tract haemorrhage in severe EB patients. CONCLUSION: Severe EB-complicated lower digestive tract haemorrhage is a critical condition in burns, which usually have deep wounds with severe infection surfaces that are difficult to deal with. Enteroscopic haemostasis in controlling lower digestive tract haemorrhage is usually ineffective. Clinical experiences indicate that early management of the wound with effective preventive and therapeutive measures for infection control may be a good choice in the prevention and treatment of lower digestive tract haemorrhage leading to improvement in its prognosis.

Transplantation of epidermis of scar tissue on acellular dermal matrix.

This study enrolled 22 participants with hypertrophic scarring after burn who received treatment with co-transplantation of acellular dermal matrix and epidermis of either normal skin or scar tissue. Scar thickness was evaluated with high frequency ultrasonography and the distribution of keratinocyte stem cells was detected by immunostaining. The results showed p63-positive keratinocyte stem cells throughout the epidermis of scar tissue. However, if co-transplanted on acellular dermal matrix, this effectively inhibited scar formation and pruritus, providing an alternative method to treat hypertrophic scarring.

Tec kinase mediating IL-8 transcription in monocytes stimulated with LPS.

The purpose of present study was to explore the possibility of Tec kinase as a mediator for IL-8 transcription in monocytes stimulated with LPS. Plasmids of mouse Tec kinase IV or Tec kinase IV with inactivating point mutations generated with QuikChange site-directed mutagenesis were co-transfected with IL-8 promoter driven luciferase construct into RAW264.7 cells, then luciferase activity was measured with a luminometer. The results shown Tec kinase could significantly enhance IL-8 transcription. Furthermore, point inactivating mutation in SH2, PH or PTK domain almost completely abolish the effects of Tec kinase on the transcription of IL-8. In the transfection experiment, PD98059, a MEK1 inhibitor, decreased the transcription of IL-8 in a dose dependent pattern. When siRNA for Tec kinase was transfected into THP-1 cells, it could efficiently block the production of IL-8 from THP-1 cells (p < 0.01) stimulated with LPS. In conclusion, Tec kinase may mediate the transcription of IL-8 in monocyte stimulated with LPS.

[Postburn change in the plasma level of neuron specific enolase in burned patients with cerebral malfunction].

OBJECTIVE: To explore the relationship between the change in neuron specific enolase (NSE) and brain malfunction in burned patients. METHODS: The serum samples of 11 burned patients with brain dysfunction were collected for the development of the serum level of neuron specific enolase with radioimmunoassay, and the correlation between condition of systemic inflammation and the levels of neuron specific enolase was assessed. RESULTS: The level of NSE in burn patients with cerebral malfunction was obviously higher than that in control, and the level was correlated with the systemic inflammation. CONCLUSION: The change in the level of serum NSE could reflect the damage degree of central nervous system to some extent.

Expression and regulation of vascular cell adhesion molecule-1 in human umbilical vein endothelial cells induced by sera from severely burned patients.

OBJECTIVE: The purpose of this study was to determine the expression and regulation of vascular cell adhesion molecule (VCAM)-1 in human umbilical vein endothelial cells (HUVECs) induced by sera from severely burned patients. DESIGN: Controlled laboratory study. SETTINGS: Research laboratory in a university hospital. SUBJECTS: HUVECs. INTERVENTIONS: HUVECs were incubated with serum from eight healthy controls and eight patients with thermal injuries of >50% total body surface area. The experiment was repeated after pretreatment with pyrrolidine dithiocarbamate, an inhibitory effect on nuclear factor-kappaB activation, SB203580, a specific p38 mitogen-activated protein kinase inhibitor, and PD98059, a mitogen-activated protein/extracellular signal-regulated kinase inhibitor. MEASUREMENTS AND MAIN RESULTS: Protein and messenger RNA expression of VCAM-1 was measured by flow cytometry and reverse transcription-polymerase chain reaction respectively. Soluble VCAM-1 level in HUVECs culture supernatants was measured by enzyme-linked immunosorbent assay. Sera from severely burned patients showed a stimulatory effect on VCAM-1 messenger RNA levels and an increased VCAM-1 expression on the endothelial cell surfaces. The soluble form of VCAM-1 molecules was also elevated by the stimulation of burn sera. In vitro peripheral blood mononuclear leukocytes adherence to HUVECs incubated with burn sera was significantly increased compared with those incubated with control sera. Finally, these events were significantly inhibited by pretreatment with antioxidants pyrrolidine dithiocarbamate or SB203580, whereas PD98059 had no significant effect. CONCLUSIONS: These findings suggest that sera from severely burned patients induced up-regulation of VCAM-1 expressions in HUVECs, and this process might be largely dependent on oxidant-mediated nuclear factor-kappaB activation and p38 mitogen-activated protein kinase pathways.

[Mechanism of p38 mitogen-activated protein kinase in postburn acute pulmonary injury in scalded rats].

OBJECTIVE: To investigate the role of p38 mitogen-activated protein kinase (MAPK) signal transduction pathway in the production of the proinflammatory factors such as tumor necrosis factor (TNF-alpha) and interleukin 1beta (IL-1beta) in lungs and in the pulmonary endothelial cell injury in severely scalded rats. METHODS: Forty eight adult healthy SD rats were randomly divided into three groups with 16 rats in each group, i.e. sham, burn and burn with SB203580 treatment groups. The changes in the TNF-alpha and IL-1beta contents in serum and bronchoalveolar lavage fluid (BALF), the von Willebrand factor (vWF) contents in plasma and pulmonary microvessels and pulmonary activating protein (AP-1) activity were determined at 24 postburn hours (PBH). RESULTS: Compared with those in sham group, the TNF-alpha and IL-1beta contents in serum and BALF and the vWF content in plasma (194.2% +/- 28.3% vs 93.2% +/- 14.3%) at 24 PBH in burn group increased significantly (P < 0.01), whereas vWF content in pulmonary microvessel decreased obviously (1.1 +/- 0.3 vs 3.3 +/- 0.4, P < 0.01). In addition, the pulmonary AP-1 activity also increased at 24 PBH. Nevertheless, all the above indices improved obviously in burn with SB203580 (inhibitor of p38 MAPK signal transduction pathway) treatment group when compared with those in burn group. CONCLUSION: AP-1 might mediate the production of proinflammatory factors, such as TNF-alpha and IL-1beta in lungs leading to pulmonary vascular endothelial injury, after being activated by activated p38 MAPK.