A novel BAFF antagonist, BAFF-Trap, effectively alleviates the disease progression of systemic lupus erythematosus in MRL/lpr mice.

Abnormal B cells, which produce antibodies against self-antigens, play a key role in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). B-cell activating factor (BAFF) is closely associated with abnormal B cells and participates in B cell-mediated autoimmune diseases; thus, neutralizing BAFF is an effective method for treating these diseases. Our group designed a novel fusion protein, BAFF-Trap, that contains the BAFF-binding domains of two BAFF receptors (TACI and BAFF-R) and the Fc domain of human IgG1. In this study, we showed that BAFF-Trap significantly decreased the autoantibody levels, BAFF concentrations and B cells numbers in MRL/lpr mice. BAFF-Trap suppressed the expression of pro-inflammatory cytokines in the kidney and decreased the frequencies of T cell subsets and dendritic cells. Furthermore, BAFF-Trap reduced proteinuria and IgG deposition, relieved glomerular damage in the kidney, and markedly improved the survival rate of mice. These results indicated that BAFF-Trap may be a potential drug for the treatment of SLE.

Prevotella copri is associated with carboplatin-induced gut toxicity.

As a widely used cancer drug, carboplatin often results in serious side effects, such as gut toxicity. In this study, we examined the effects of gut microbiota on mice with carboplatin-induced intestinal mucosal damage. Carboplatin resulted in intestinal mucositis, as indicated by weight loss, diarrhoea, and infiltration of inflammatory cells. It markedly increased the expression of inflammatory cytokines/chemokines in intestine. Carboplatin also altered the diversity and composition of the gut microbiota. A significantly higher abundance of Prevotella copri (P. copri) was observed in carboplatin-treated mice. Moreover, the content of P. copri was positively correlated with the severity of intestinal mucositis. Pretreatment with metronidazole reduced the content of P. copri and relieved the intestinal mucosal injury and inflammation that was induced by carboplatin. Further study revealed that supplementation with P. copri in carboplatin-treated mice resulted in more severe tissue damage, lower tight junction protein expression and higher cytokine expression, and it enhanced both local and systemic immune responses. These data demonstrated that P. copri was involved in the pathological process of carboplatin-induced intestinal mucositis, suggesting a potential attenuation of carboplatin-induced intestinal mucositis by targeting P. copri.

Nano-drug delivery systems in wound treatment and skin regeneration.

Skin damages are defined as one of most common lesions people suffer from, some of wounds are notoriously difficult to eradicate such as chronic wounds and deep burns. Existing wound therapies have been proved to be inadequate and far from satisfactory. The cutting-edge nanotechnology offers an unprecedented opportunity to revolutionize and invent new therapies or boost the effectiveness of current medical treatments. In particular, the nano-drug delivery systems anchor bioactive molecules to applied area, sustain the drug release and explicitly enhance the therapeutic efficacies of drugs, thus making a fine figure in field relevant to skin regeneration. This review summarized and discussed the current nano-drug delivery systems holding pivotal potential for wound healing and skin regeneration, with a special emphasis on liposomes, polymeric nanoparticles, inorganic nanoparticles, lipid nanoparticles, nanofibrous structures and nanohydrogel.

Therapeutic effects of a novel BAFF blocker on arthritis.

B-cell targeted therapy is effective for autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis (RA), although there are setbacks in RA clinical trials. In this study, we designed a novel B-cell activating factor (BAFF) antagonist: BAFF-Trap, a recombinant glycoprotein with BAFF-binding domains of two BAFF receptors (TACI and Br3) linked to Fc domain of human IgG1. Unlike TACI-Fc, BAFF-Trap bound BAFF but not APRIL (a proliferation-inducing ligand), and significantly suppressed the development of collagen-induced arthritis and adjuvant-induced arthritis. Furthermore, BAFF-Trap inhibited proinflammatory cytokine expression, ameliorated joint damage and suppressed B- and T-cell activation. BAFF-Trap reduced dendritic cells in joints, and increased regulatory T cell, regulatory B-cell, and M2 macrophage. The function of BAFF-Trap was related to inhibition of canonical and noncanonical NF-κB activation. Thus, BAFF-Trap may be a valuable agent for the effective treatment of RA.

A dual deformable liposomal ointment functionalized with retinoic acid and epidermal growth factor for enhanced burn wound healing therapy.

An ointment containing retinoic acid deformable liposomes (TRA DLs) and epidermal growth factor cationic deformable liposomes (EGF CDLs) was prepared for the treatment of deep partial-thickness burns. The characterization tests confirmed both liposomes featured small particle sizes, high drug entrapment efficiencies and sustained drug release behavior. Compared with the free drug, TRA DLs and EGF CDLs exhibited superior skin permeation and remarkably increased drug deposition by 2.9 and 18.8 folds, respectively. Results on HaCaT cells indicated the combined application of two liposomes exerted a synergistic effect and prominently promoted cell proliferation and migration. Application of the dual liposomal ointment on a deep partial-thickness burn model stimulated wound closure (p < 0.001), promoted skin appendage formation and increased collagen production, thus improving healing quality. Finally, it was demonstrated that TRA significantly up-regulated the expression of EGFR and HB-EGF to enhance the therapeutic effect of EGF. Therefore, the dual liposomal ointment is a promising topical therapeutic for burn treatment.

Hydrogen peroxide-inactivated bacteria induces potent humoral and cellular immune responses and releases nucleic acids.

The problem of nosocomial infection is seriously escalating. Bacterial vaccines are indispensable for preventing infections caused by multi-drug resistant organisms. Some researchers have put forward the use of hydrogen peroxide (H2O2) as a new technology platform for virus deactivation. This deactivated virus can induce the number of CD8+ T lymphocytes, which can enhance antiviral responses. Although, H2O2 treatment has been rarely reported on the exploration of bacterial deactivation, H2O2 deactivation of whole-cell bacteria could be a potential novel approach for bacterial vaccine development. Here we present a strategy for H2O2-deactivated bacterial whole-cell vaccines, for two major pathgens, Pseudomonas aeruginosa and Staphylococcus aureus. The proactive effects of vaccination were assessed in vitro and in vivo. H2O2-deactivation of bacterial vaccines retains more complete epitopes and exhibits lower toxicity, as compared to formaldehyde, a conventional deactivator that was investigated in this study. Furthermore, H2O2-deactivated bacterial vaccines induce anti-infection responses through enhancement of humoral immunity and cellular immunity. Vaccination with H2O2-deactivated whole-cell bacteria in mice mainly elicits whole-cell specific antibody titers and balances the IgG2a and IgG1 response, predominantly with IgG3 induction at the later stages, meanwhile provides opsonic protection against challenge with pathogens. Finally, H2O2 deactivation of bacteria has been found to cause the release of bacterial DNA which is followed by NF-κB activation. These findings demonstrate that the deactivation of whole-cell bacteria with H2O2 is potentially advantageous for immune responses. Considering the prevention of drug-resistant infections, this deactivation method could be simultaneously applied as an innovative strategy for bacterial vaccine development.

Novel Self-Assembled Micelles Based on Cholesterol-Modified Antimicrobial Peptide (DP7) for Safe and Effective Systemic Administration in Animal Models of Bacterial Infection.

Owing to their broad-spectrum antibacterial properties, multitarget effects, and low drug resistance, antimicrobial peptides (AMPs) have played critical roles in the clinical therapy of drug-resistant bacterial infections. However, the potential hazard of hemolysis following systemic administration has greatly limited their application. Here, we developed a novel AMP derivative, DP7-C, by modifying a formerly identified highly active AMP (DP7) with cholesterol to form an amphiphilic conjugate. The prepared DP7-C easily self-assembled into stable nanomicelles in aqueous solution. The DP7-C micelles showed lower hemolytic activity than their unconjugated counterparts toward human red blood cells and a maximum tolerated dose of 80 mg/kg of body weight in mice via intravenous injection, thus demonstrating improved safety. Moreover, by eliciting specific immunomodulatory activities in immune cells, the DP7-C micelles exerted distinct therapeutic effects in zebrafish and mouse models of infection. In conclusion, DP7-C micelles may be an excellent candidate for the treatment of bacterial infections in the clinic.

Induction and Amelioration of Methotrexate-Induced Gastrointestinal Toxicity are Related to Immune Response and Gut Microbiota.

As a widely used anticancer and immunosuppressive agent, methotrexate (MTX) can induce multiple adverse drug reactions (ADRs), such as gastrointestinal toxicity, the mechanisms are poorly understood. Gut microbiota has been widely reported to be associated with the onset of multiple diseases as well as treatment outcomes of different drugs. In this study, mucosal injury was observed in MTX-treated mice, leading to significant changes in macrophages (i.e., M1/M2 ratio, P < 0.05) but not in dendritic cells. Moreover, the population, diversity and principal components of the gut microbiota in mice were dramatically altered after MTX treatment in a time-dependent manner, and Bacteroidales exhibited the most distinct variation among all the taxa (P < 0.05). Bacteroides fragilis was significantly decreased with MTX treatment (P < 0.01) and tended to decrease proportionately with increasing macrophage density. Gavage of mice with B. fragilis ameliorated MTX-induced inflammatory reactions and modulate macrophage polarization. In conclusion, our results delineate a strong impact of the gut microbiota on MTX-induced intestinal mucositis and provide a potential method for the prevention of such ADRs.

Delivery of a Modified mRNA Encoding IL-22 Binding Protein (IL-22BP) for Colon Cancer Gene Therapy.

As an alternative form of genetic material, mRNA lacks a CpG island and can function without crossing the nuclear membrane. These properties make mRNA less of a potential immune stimulant than plasmid DNA. Therefore, chemically modified mRNA is an effective alternative to plasmid DNA for gene therapy. In this study, cationic liposomes were used as a vector to transport mRNA complexes that had been compressed using protamine and to obtain high mRNA transport and expression efficiency. The liposome-protamine-IL-22BP mRNA complex can strongly inhibit the growth of C26 tumour cells by inducing apoptosis, inhibiting tumour angiogenesis and increasing the number of immune cells that infiltrate the tumour microenvironment. The obvious tumour regression and safety of this approach were observed in peritoneal metastasis and subcutaneous xenograft models. The antitumour effect of the liposome protamine mRNA complex was as good as that for a plasmid DNA complex, and demonstrated the potential for mRNA-based gene therapy.

The novel complex combination of alum, CpG ODN and HH2 as adjuvant in cancer vaccine effectively suppresses tumor growth in vivo.

Single-component adjuvant is prone to eliciting a specific type of Th1 or Th2 response. So, the development of combinatorial adjuvants inducing a robust mixed Th1/Th2 response is a promising vaccination strategy against cancer. Here, we describe a novel combination of aluminum salts (alum), CpG oligodeoxynucleotide (CpG) and innate defense regulator peptide HH2 for improving anti-tumor immune responses. The CpG-HH2 complex significantly enhanced the production of IFN-γ, TNF-α and IL-1ß, promoted the uptake of antigen and strengthened the activation of p38, Erk1/2 and NF-κB in vitro, compared to CpG or HH2 alone. Immunization with NY-ESO-1 antigen plus alum-CpG-HH2 combinatorial adjuvant effectively inhibited tumor growth and reduced tumor burden in prophylactic and therapeutic tumor models and even in passive serum or cellular therapy. In addition, co-administration of NY-ESO-1 with alum-CpG-HH2 combinatorial adjuvant markedly activated NK cell cytotoxicity, induced antibody-dependent cellular cytotoxicity (ADCC), dramatically elicited cytotoxic T lymphocytes (CTLs) response, and increased infiltrating lymphocytes in tumors. Moreover, in vivo depletion of CD8+ T cells completely and depletion of NK cells partially blocked the anti-tumor activity of NY-ESO-1-alum-CpG-HH2 immunization. Overall, our results demonstrate a novel adjuvant combination for cancer vaccine with efficient immunomodulation by stimulating innate immunity and mediating adaptive immunity.

Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria.

Antibiotic-resistant bacteria present a great threat to public health. In this study, the synergistic effects of antimicrobial peptides (AMPs) and antibiotics on several multidrug-resistant bacterial strains were studied, and their synergistic effects on azithromycin (AZT)-resistance genes were analyzed to determine the relationships between antimicrobial resistance and these synergistic effects. A checkerboard method was used to evaluate the synergistic effects of AMPs (DP7 and CLS001) and several antibiotics (gentamicin, vancomycin [VAN], AZT, and amoxicillin) on clinical bacterial strains (Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli). The AZT-resistance genes (ermA, ermB, ermC, mefA, and msrA) were identified in the resistant strains using quantitative polymerase chain reaction. For all the clinical isolates tested that were resistant to different antibiotics, DP7 had high antimicrobial activity (≤32 mg/L). When DP7 was combined with VAN or AZT, the effect was most frequently synergistic. When we studied the resistance genes of the AZT-resistant isolates, the synergistic effect of DP7-AZT occurred most frequently in highly resistant strains or strains carrying more than two AZT-resistance genes. A transmission electron microscopic analysis of the S. aureus strain synergistically affected by DP7-AZT showed no noteworthy morphological changes, suggesting that a molecular-level mechanism plays an important role in the synergistic action of DP7-AZT. AMP DP7 plus the antibiotic AZT or VAN is more effective, especially against highly antibiotic-resistant strains.

Early and Thorough Wound Debridement Is Crucial for Treatment of Patients With Thermal Burns and para-Chloronitrobenzene Poisoning.

para-Chloronitrobenzene (p-CNB) is one of the important chemicals with high liposolubility and oxidizing properties. Heated p-CNB liquid can cause thermal injury by absorption over skin and wound and even methemoglobinemia by conversion of hemoglobin into methemoglobin. Severe methemoglobinemia is a life-threatening condition that demands immediate treatment. It is very rare for individuals to be injured by heated p-CNB, but they should be carefully attended to because of the peculiarities of this kind of injury. In the past 10 years, we received 5 patients who were injured by heated p-CNB. In addition to the intravenous administration of methylene blue, prompt and thorough wound management played a crucial role in the treatment of these critically ill patients, indicating the potential value of sufficient information for the clinical practitioners. The purpose of this article is to report our experience in the management of patients with thermal burns and p-CNB poisoning.

Synthetic innate defense regulator peptide combination using CpG ODN as a novel adjuvant induces long­lasting and balanced immune responses.

Vaccines are critical tools for the prevention and treatment of several diseases. Adjuvants have been traditionally used to enhance immunity to vaccines and experimental antigens. In the present study, the adjuvant combination of CpG oligodeoxynucleotides (CpG ODN) and the innate defense regulator (IDR) peptide, IDR­HH2, was evaluated for its ability to enhance and modulate the immune response when formulated with alum and the recombinant hepatitis B surface antigen (HBsAg). The CpG­HH2 complex enhanced the secretions of tumor necrosis factor­α, monocyte chemotactic protein 1 and interferon­Î³ by human peripheral blood mononuclear cells and promoted murine bone marrow dentritic cell maturation. In addition, the present study demonstrated that IDR­HH2 was chemotactic for human neutrophils, THP­1 cells and RAW264.7 cells at concentrations between 2.5 and 40 µg/ml. The present study also observed that significantly higher anti­HBs antibody titers, which were sustained at high levels for as long as 35 weeks following the boost immunization, were induced by the combination adjuvant, even when co­administered with a commercial hepatitis B vaccine at a low antigen dose (0.1 µg HBsAg). Notably, the level of IgG2a was almost equal to the level of IgG1, indicating that a balanced T helper (Th)1/Th2 immune response was elicited by the novel vaccine, which was consistent with the ELISpot results. These data suggest that the CpG­HH2 complex may be a potential effective adjuvant, which facilitates a reduction in the dose of antigen and induces long­lasting, balanced immune responses.

Development of a Recombinant Xenogeneic Tumor Necrosis Factor Alpha Protein Vaccine To Protect Mice from Experimental Colitis.

Previous studies have highlighted the efficacy of tumor necrosis factor alpha (TNF-α) inhibitors, including monoclonal antibodies and soluble receptors, in the treatment and management of intestinal bowel disease (IBD). However, because of the immunogenicity of xenogeneic TNF-α inhibitors, antidrug antibodies (ADAs) can be triggered after repeated administration. An alternative way to target TNF-α is active immunization to elicit the production of high titers of neutralizing antibodies. In this study, we prepared a xenogeneic TNF-α protein vaccine and studied the protective effects in experimental colitis models. The xenogeneic TNF-α protein vaccine could overcome self-tolerance and induce TNF-α-specific neutralizing antibody. Moreover, the xenogeneic TNF-α protein vaccine could protect mice from acute and chronic colitis induced by dextran sodium sulfate (DSS). One possible explanation for this protective effect is the production of TNF-α-specific neutralizing antibody, which absorbed the biological activity of mouse TNF-α (mTNF-α) and failed to induce T lymphocyte apoptosis. In summary, use of the xenogeneic TNF-α protein vaccine may be a potent therapeutic strategy for IBD.

The characteristics and correlation between the ischemia-reperfusion and changes of redox status in the early stage of severe burns.

OBJECTIVE: Both the ischemia-reperfusion injury and the abnormal changes of redox status are the important pathologic changes in the burn shock stage for severe burns. The study of clinical dynamic, quantitative relevance about them was performed. METHODS: In this study, blood redox potential (ORP) values (ΔORP value was adopted, as the quantitative index to reflect the overall redox status), plasma uric acid levels (important antioxidant, as antioxidant index), and the burn shock state-related indicators (lactic acid and hematocrit) of 48 burn patients were dynamically, quantitatively monitored during the early stage after injury. RESULTS: The results revealed that the duration of abnormal fluctuation of redox status in the early stage of severe burns was longer than that of the traditional clinical shock stage (2-3 days). The changes of overreduction soon after injury were closely related to the hypovolemia-related hypoxia, and the following overoxidation status was consistent with the pathophysiological changes related to the reperfusion, and the degrees of variation were closely related to the severity of burn injury and prognosis. Moreover, early surgery (3 days after injury) had no significant influence on the changing trend of abnormal redox status in the early stage of severe burns. CONCLUSION: The ischemia-reperfusion injury caused by burn shock appears the main factor contributing to the abnormal biphasic changes of redox status in the early stage of severe burns. Our findings provide useful information for the redox regulation treatment for burn shock.

Effective inhibition of melanoma tumorigenesis and growth via a new complex vaccine based on NY-ESO-1-alum-polysaccharide-HH2.

BACKGROUND: A safe and effective adjuvant plays an important role in the development of a vaccine. However, adjuvants licensed for administration in humans remain limited. Here, for the first time, we developed a novel combination adjuvant alum-polysaccharide-HH2 (APH) with potent immunomodulating activities, consisting of alum, polysaccharide of Escherichia coli and the synthetic cationic innate defense regulator peptide HH2. METHODS: The adjuvant effects of APH were examined using NY-ESO-1 protein-based vaccines in prophylactic and therapeutic models. We further determined the immunogenicity and anti-tumor effect of NY-ESO-1-APH (NAPH) vaccine using adoptive cellular/serum therapy in C57/B6 and nude mice. Cell-mediated and antibody-mediated immune responses were evaluated. RESULTS: The APH complex significantly promoted antigen uptake, maturation and cross-presentation of dendritic cells and enhanced the secretion of TNF-α, MCP-1 and IFN-γ by human peripheral blood mononuclear cells compared with individual components. Vaccination of NAPH resulted in significant tumor regression or delayed tumor progression in prophylactic and therapeutic models. In addition, passive serum/cellular therapy potently inhibited tumor growth of NY-ESO-1-B16. Mice treated with NAPH vaccine produced higher antibody titers and greater antibody-dependent/independent cellular cytotoxicity. Therefore, NAPH vaccination effectively stimulated innate immunity, and boosted both arms of the adaptive humoral and cellular immune responses to suppress tumorigenesis and growth of melanoma. CONCLUSIONS: Our study revealed the potential application of APH complex as a novel immunomodulatory agent for vaccines against tumor refractory and growth.

In vitro and in vivo activities of antimicrobial peptides developed using an amino acid-based activity prediction method.

To design and discover new antimicrobial peptides (AMPs) with high levels of antimicrobial activity, a number of machine-learning methods and prediction methods have been developed. Here, we present a new prediction method that can identify novel AMPs that are highly similar in sequence to known peptides but offer improved antimicrobial activity along with lower host cytotoxicity. Using previously generated AMP amino acid substitution data, we developed an amino acid activity contribution matrix that contained an activity contribution value for each amino acid in each position of the model peptide. A series of AMPs were designed with this method. After evaluating the antimicrobial activities of these novel AMPs against both Gram-positive and Gram-negative bacterial strains, DP7 was chosen for further analysis. Compared to the parent peptide HH2, this novel AMP showed broad-spectrum, improved antimicrobial activity, and in a cytotoxicity assay it showed lower toxicity against human cells. The in vivo antimicrobial activity of DP7 was tested in a Staphylococcus aureus infection murine model. When inoculated and treated via intraperitoneal injection, DP7 reduced the bacterial load in the peritoneal lavage solution. Electron microscope imaging and the results indicated disruption of the S. aureus outer membrane by DP7. Our new prediction method can therefore be employed to identify AMPs possessing minor amino acid differences with improved antimicrobial activities, potentially increasing the therapeutic agents available to combat multidrug-resistant infections.

Ad-endostatin treatment combined with low-dose irradiation in a murine lung cancer model.

Radiation therapy is a conventional strategy for treating advanced lung cancer yet is accompanied by serious side-effects. Its combination with other strategies, such as antiangiogenesis and gene therapy, has shown excellent prospects. As one of the potent endogenous vascular inhibitors, endostatin has been widely used in the antiangiogenic gene therapy of tumors. In the present study, LL/2 cells were infected with a recombinant adenovirus encoding endostatin (Ad-endostatin) to express endostatin. The results showed that LL/2 cells infected with the Ad-endostatin efficiently and longlastingly expressed endostatin. In order to further explore the role of Ad-endostatin combined with irradiation in the treatment of cancer, a murine lung cancer model was established and treated with Ad-endostatin combined with low-dose irradiation. The results showed that the combination treatment markedly inhibited tumor growth and metastasis, and prolonged the survival time of the tumor-bearing mice. Furthermore, this significant antitumor activity was associated with lower levels of microvessel density and anoxia factors in the Ad-Endo combined with irradiation group, and with an increased apoptotic index of tumor cells. In addition, no serious side-effects were noted in the combination group. Based on our findings, Ad-endostatin combined with low-dose irradiation may be a rational alternative treatment for lung cancer and other solid tumors.

The reliability of clinical dynamic monitoring of redox status using a new redox potential (ORP) determination method.

PURPOSE: Quantitative monitoring of the redox status is the foundation for redox-related treatment. The purpose of this study was to evaluate the reliability of a new depolarization curve method for plasma redox potential (ORP) monitoring. METHODS: Using the new method, we performed redox determinations for the first time under different sample-handling conditions, including redox titration experiments using KMnO4 and vitamin C and dynamic redox monitoring in burn patients. The relative ORP value (ΔORP) method (improved traditional method) was used as the reference. RESULTS: The new method's better reliability, electrochemical specificity and practicability, and known group validity, which are closely associated with the redox-related pathological processes of severe burns, were confirmed. Furthermore, bidirectional change in the redox status in severe burn patients was also observed for the first time. CONCLUSIONS: This simple, stable new method could be a better practical tool for making the dynamic monitoring of the redox status feasible and for providing useful quantitative information for the judgment of redox-related pathological process, thus improving corresponding individualized treatments that rely on quantitative adjustments to the redox status.

[Change in sliver metabolism after the application of nanometer silver on burn wound].

OBJECTIVE: To investigate the change in silver metabolism after the application of nanometer silver on burn wound. METHODS: Twenty-six burn patients with partial thickness burn covering 6-12% TBSA were enrolled in the study as treatment group (T), and 30 healthy adult volunteers as control group (C). Burn wound covering 5% TBSA was covered with nanometer silver dressing for 5 days. The silver contents in the serum and urine in C group of people and in T group of patients at different time points before and after the application of nanometer silver were measured by atomic absorption spectrum method. The hepatic and renal function was also monitored on the 7th and 14th post treatment days (PTD) after silver application. Tissue samples from the wound and wound edge 14 days after silver application were harvested for the determination of silver content by plumbago stove and atomic absorption spectrum. The silver deposition was also detected by transmission electronic microscope. RESULTS: Compared to those in C group, the silver contents in serum and urine in T group increased on 3rd and 5th PTD, but decreased to the normal level on 14th PTD. Mild hepatic dysfunction occurred in 7 cases on 7 PTD, whereas the renal function remained normal. The tissue mass percentage of silver in burn wound and wound edge was (0.7 +/- 0.1) x 10(-6), but no silver deposition in tissue was observed by transmission electron microscope. CONCLUSION: It was proved to be safe to have the nanometer silver dressing applied on partial thickness burn wound of middle and small areas.