ABSTRACT
Aim To investigate the effects of different species Fc receptors (FcRn) on pharmacokinetic characteristics of MIL94, a monoclonal antibody against West Nile virus developed by Academy of Military Sciences, which has a neutralizing effect on West Nile virus and whose maintenance time in vivo is closely related to its antiviral effect. Methods The pharmacokinetic characteristics of MIL94 in mice expressing FcRn of different species (wild-type mice, hFcRn mice and FcRn knockout mice) were compared-. Wild-type mice and FcRn knockout mice were injected intravenously with MIL94 respectively. HFcRn mice were randomly divided into four groups. Two groups were injected intravenously with MIL94, and the other two groups were injected intravenously with intravenous immunoglobulin (IVIG) and then intravenously with MIL94. Indirect ELISA was used to determine the MIL94 concentration in mouse serum. WinNonlin software was used to calculate the pharmacokinetic parameters. Results After intravenous injection with MIL94, the in vivo pharmacokinetics were basically linear. The distribution volume of MIL94 in animals was related to FcRn. The half-life in vivo varied greatly between different groups. Conclusions FcRn can affect the half-life of MIL94 in different species mainly via alternation of its elimination and distribution. It is expected that the half-life of FcRn in human will be longer than that in preclinical animals.
ABSTRACT
Aim To investigate the effects of YL- IPA08 on the endogenous metabolites of PTSD model rats by metabolomics methods, and to explore the metabolic pathways and possible mechanisms of YL-IPA08 against PTSD. Methods The rats were randomly divided into control group, PTSD model group, and administration group of PTSD rats induced by forced swimming test, and the treatment group was given YL- IPA08 (2 mg • kg"1) by intragastric gavage for 15 consecutive days. High-performance liquid chromatog- raphy-mass spectrometry (HPLC-MS/MS) technology was used to detect the endogenous differential metabolites and the associated metabolic pathways in rat plasma samples. Targeted quantitative technology was simultaneously applied to detect the concentrations of 18 bile acids in rat plasma. Results Compared with control group, 40 kinds of endogenous metabolites including glutamic acid, proline, valine, arginine, leucine , cholic acid, and creatine showed significant difference, and the concentrations of 11 bile acids significantly increased in plasma of model group as well. Compared with model group, after YL-IPA08 intervention , the above-mentioned potential metabolites ap-peared to return to normal levels. Conclusions Metabolomics analysis reveals that YL-IPA08 has intervention effect on PTSD model rats. The mechanism may be related to the regulation of amino acid metabolism and bile acid metabolism.
ABSTRACT
Objective:To explore the difference in the therapeutic effect of stamp skin and meek skin on wound repair in patients with extensive burns.Methods:A total of 81 patients with extensive burn from March 2016 to February 2018 in 73th Army Hospital of PLA were selected and divided into group A (stamp skin grafting, 35 cases) and group B (meek skin grafting, 46 cases) according to the choice of wound repair methods before operation. The survival and healing conditions, treatment costs, mortality and rehabilitation of the two groups were compared.Results:There was no significant difference in the survival rate, wound healing rate and mortality between group A and group B (82.86% vs 86.96%, 5.71% vs 8.70%, P>0.05). The survival rate of skin graft in group A was higher than that in group B, and the wound healing time and treatment cost of 1% total body surface area (TBSA) in group A were lower than those in group B [(76.3±5.1)% vs (67.9±6.2)%, (41.5±4.9)d vs (45.8±5.1)d, (1 215.6±235.1)yuan vs (7 689.5±681.0)yuan, P<0.05]. The excellent and good rate of rehabilitation in group A was significantly lower than that in group B (68.57% vs 86.96%, P<0.05). Conclusions:The application of the stamp skin in the repair of wounds in large-area burn patients has a higher flap survival rate than meek skin repair, which can shorten the healing time of the flap and reduce the treatment cost, but the rehabilitation effect is poor.
ABSTRACT
Objective To express and purify the recombinant UL7 protein of herpes simplex virus 1 (HSV-1), to prepare the corresponding UL7-specific polyclonal antibody and to preliminarily analyze the expression of UL7 protein during the proliferation of HSV-1. Methods The UL7 gene was amplified by PCR and then cloned into the pGEX-5X-1 vector for expression of UL7 protein in the prokaryotic expression system. The constructed expression plasmid, pGEX-5X-1-UL7, was transformed into E. coli BL21 (DE3) to induce the expression of UL7 protein by IPTG. The purified GST-UL7 fusion protein was used as antigen to inject the ICR mouse for the preparation of polyclonal antibody specific for UL7 protein. The titer and speci-ficity of the polyclonal antibody were analyzed by using indirect ELISA and Western blot assay, respectively. The UL7 protein-specific polyclonal antibody was used to detect the expression of UL7 protein at different time points after infecting Vero cells with HSV-1. Results The GST-UL7 fusion protein was efficiently ex-pressed in E. coli BL21 (DE3). The UL7 protein-specific polyclonal antibody was prepared with high titer (1 ∶ 105) and high specificity as indicated by the indirect ELISA and Western blot assay. The expression of UL7 protein was detected at different time points after infecting Vero cells with HSV-1. Conclusion The GST-UL7 fusion protein was obtained successfully and the UL7 protein-specific polyclonal antibody was pre-pared. Accompany with the proliferation of HSV-1, the expression of UL7 protein was detected at different time points by using the polyclonal antibody.
ABSTRACT
Objective To explore the effect of damage control surgery (DCS) in the treatment of severe electric burn. Methods Retrospective analysis on clinical data of 45 patients with severe electric burn was con-ducted. According to implementing DCS or not , patients were separated into DCS group and control group. In DCS group, tangential excision and transplanted xenogenic acellular dermal matrix was conducted for severe electric burn cases with deep Ⅱ degree wound, and escharectomy and VSD dressing for Ⅲ~Ⅳ degree electric contact burn wound at the first stage then skin-grafting or skin flap-grafting on the secong stage was applied. For control group , debridement, tangential excision or escharectomy and skin-grafting or skin flap-grafting to close the wound were conducted. We compared the difference in terms of operation time, length of stay, disability rate, mortality and complications between 2 groups. Results The operation time, incidince of disability and complications in DCS Group obviously decreased but there was no difference in length of stay and mortality in both groups. Conclusion DCS is effective for reducing complications and optimizing therapeutic effect for severe electric burn patients.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate angiogenesis of collagen-chitosan porous scaffold, and to study survive of skin grafts on the scaffold after bilayer dermal equivalent (BDE) was transplanted on wounds with full thickness skin defects.</p><p><b>METHODS</b>The full thickness skin defects were made on 10 Bama miniature pigs and the BDE composed of collagen-chitosan porous scaffold and silicone membrane was transplanted on wound. Angiogenesis in dermal equivalent, wound healing, and healing and survive of skin grafts on dermal equivalent were observed in 1, 2, and 3 weeks after the BDE transplantation. At the same time, CD34 positive signals (neo-forming micro-vessels) were detected by immunohistochemical staining.</p><p><b>RESULTS</b>Inflammatory cells and fibroblasts infiltrated into dermal equivalent and a few new micro-vessels had been formed in 1 week after the BDE transplantation; neo-forming micro-vessels perpendicular to wound bed had increased significantly in 2 weeks after the BDE transplantation; neo-forming micro-vessels could be observed in almost all dermal equivalents in 3 weeks after the BDE transplantation. CD34 positive signals (neo-forming micro-vessels) in 3 weeks after the BDE transplantation was much more than those in 2 weeks after the BDE transplantation, and CD34 positive signals in 2 weeks after the BDE transplantation was much more than those in 1 week after the BDE transplantation. Survival rate of intermediate split thickness skin graft were 10%, 70% and 100% respectively after the skin grafts had been grafted for 2 weeks on surface of the scaffold which had been transplanted for 1, 2 and 3 weeks. Epidermis which had been grafted on surface of the scaffold for 1 or 2 weeks could perfectly survive after BDE had been transplanted for 1 or 2 weeks.</p><p><b>CONCLUSIONS</b>Collagen-chitosan porous scaffold plays a very important role in wound healing of full thickness skin defect and can induce fibroblast infiltration and new micro-vessel formation. Epidermis grafted on surface of collagen-chitosan porous scaffold can perfectly repair wounds, and it has brilliant applied prospects in repairing skin defect.</p>
Subject(s)
Animals , Female , Chitosan , Collagen , Disease Models, Animal , Graft Survival , Neovascularization, Physiologic , Silicones , Skin , Wounds and Injuries , Skin Transplantation , Swine , Swine, Miniature , Tissue Scaffolds , Wound HealingABSTRACT
<p><b>OBJECTIVE</b>To investigate biosynthetic and apoptotic mechanisms in repair of full thickness skin defect with collagen-chitosan porous scaffold transplantation, and to determinate differences between wound repair with the scaffold transplantation and scar healing without the scaffold transplantation.</p><p><b>METHODS</b>The full thickness skin defects were made on 10 Bama miniature pigs and the bilayer dermal equivalent (BDE) composed of collagen-chitosan porous scaffold and silicone membrane was transplanted on wounds. Surfaces of wounds were observed at 1, 2, and 3 weeks after the BDE transplantation, and so were done the wound repairs after epidermis had been grafted for 2 weeks on surface of the scaffold which had been transplanted on skin defect wounds for 2 weeks. At the same time, TGF-beta1 expressions, apoptosis and self collagen replacement of scaffolds in wounds were detected in situ by immunohistochemical staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) and picrosirius red polarized light. Wounds without scaffold transplantation were studied as control.</p><p><b>RESULTS</b>1) Wounds with the scaffold transplantation were different from granulation tissue. 2) The peak of TGF-beta1 expression in the scaffold wounds was from 1 to 2 weeks after BDE transplantation, and TGF-beta1 expressions decreased continuously from 3 to 4 weeks. TGF-beta1 expressions increased continuously in the control wounds from 1 to 3 weeks and decreased on 4 weeks. TGF-beta1 expressions in the scaffold wounds on 1st and 2nd week were significantly higher than those in the corresponding control wounds, whereas, TGF-beta1 expressions in the scaffold wounds on 3rd and 4th week were significantly lower than those in the corresponding control wounds. 3) Apoptosis increased continuously in the scaffold wounds from 2 to 4 weeks after BDE transplantation, and so did in the control wounds from 3 to 4 weeks. However, apoptosis signals in the scaffold wounds on 2nd, 3rd, and 4th week after BDE transplantation were significantly more than those in the corresponding control wounds, and there was no difference between apoptosis signals in the scaffold wounds on 1st week after BDE transplantation and those in the corresponding control wounds. 4) Observation by picrosirius red polarized light method: self collagen began to synthesize in the scaffold wounds on 1st week after BDE transplantation, and scaffolds had been replaced by self collagen from 2 to 3 weeks after BDE transplantation.</p><p><b>CONCLUSIONS</b>Collagen-chitosan porous scaffold plays a very important role in wound healing of full thickness skin defect. The mechanisms of wound repair by dermal scaffold are different from those by granulation and scar healing. It has a good future in repairing skin defect.</p>
Subject(s)
Animals , Female , Apoptosis , Chitosan , Metabolism , Collagen , Metabolism , Dermis , Extracellular Matrix , Skin Irritancy Tests , Skin, Artificial , Stents , Swine , Swine, Miniature , Tissue Engineering , Transforming Growth Factor beta1 , Metabolism , Wound HealingABSTRACT
<p><b>OBJECTIVE</b>To found new interface of human hepatocyte/poly propylene with good cytocompatibility for made polypropylene hollow fibers bioreactor of bioartificial liver in future.</p><p><b>METHODS</b>Using the macromolecular hydroperoxide groups on the polypropylene membrane surface as initiators, acrylamides were polymerized on the polypropylene membranes, under induction by both UV irradiation and Fe2+ reduction. Growth characteristics of human hepatocyte L-02 were detected when it was cultured on polystyrene, polypropylene and modified polypropylene membrane surface.</p><p><b>RESULTS</b>Water contact angle measurement of the polypropylene and the modified polypropylene membranes decreased from (72 +/- 5) degrees to (30 +/- 4) degrees , which indicated that the hydrophilicity of the membrane was improved obviously after the grafting modification. Human hepatocyte L-02 could not adhere and spread on modified polypropylene membrane surface, and grown in spheroidal aggregate with higher density and higher proliferation ratio measured by MTT method.</p><p><b>CONCLUSIONS</b>Acrylamide polymerized on the polypropylene membranes is a good method which not only improved human hepatocytes cytocompatibility but also found a new simple culture method with spheroidal aggregate culture of human hepatocyte.</p>
Subject(s)
Humans , Cell Culture Techniques , Methods , Cell Division , Cells, Cultured , Hepatocytes , Cell Biology , Liver, Artificial , Membranes, Artificial , Polypropylenes , Chemistry , Surface Properties , Tissue Engineering , MethodsABSTRACT
<p><b>OBJECTIVE</b>To observe the skin regeneration after hair follicle bulb cells were implanted into collagen/chitosan porous scaffolds in vitro.</p><p><b>METHODS</b>The cultured dorsal hair follicle bulb cells of 4d-old C57BL/6J mice were implanted into collagen/chitosan porous scaffolds in vitro. The skin regeneration was observed.</p><p><b>RESULT</b>The skin-like structure was formed on the collagen/chitosan porous scaffolds where were cultured the hair follicle bulb cells before 4th passages.</p><p><b>CONCLUSION</b>The skin-like structure is generated in vitro when early passages of cultured hair bulb cells are implanted into collagen/chitosan porous scaffolds.</p>