Granulocyte-Macrophage Colony-Stimulating Factor ; therapeutic use ; Humans ; Recombinant Fusion Proteins ; therapeutic use

BACKGROUNDAlthough heart transplantation has become a standard therapy for end-stage heart disease, there are few published studies regarding the use of transplant organs from marginal donors. Here we describe the clinical outcome we have obtained using marginal donor hearts.

METHODSWe analyzed 21 cases of orthotopic heart transplantation for end-stage heart disease performed in our department between September 2008 and July 2010. Of these patients, six received hearts from marginal donors and the remainder received standard-donor hearts. The two groups were compared in terms of both mortality and the incidence of perioperative complications such as infection, acute rejection, and right heart insufficiency.

RESULTSThe 1-year survival rate of both groups was 100%. Only one death was recorded in standard-donor group during follow-up. Patients who received marginal donor hearts (83%) experienced more early complications than did the standard-donor-heart group (13%), but the mortality of the two groups was the same. The duration of post-ICU stay was greater in the marginal donor group than in the standard-donor group, (35.5 ± 17.4) days and (21.7 ± 2.6) days, respectively (P < 0.05).

CONCLUSIONSThe use of marginal donor hearts increases the number of patients who can receive and benefit from transplants. However, it may introduce an increased risk of early complications, thus care should be taken both in the choice of patients who will receive marginal donor hearts and in the perioperative treatment of those for whom the procedure is performed.

Adult ; Antibodies, Monoclonal ; therapeutic use ; Female ; Heart Transplantation ; methods ; Humans ; Immunosuppressive Agents ; therapeutic use ; Male ; Methylprednisolone ; therapeutic use ; Middle Aged ; Recombinant Fusion Proteins ; therapeutic use ; Tissue Donors

Antibodies, Monoclonal ; therapeutic use ; Cell Transformation, Neoplastic ; Dexamethasone ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Glucocorticoids ; therapeutic use ; Humans ; Immunosuppressive Agents ; therapeutic use ; Lichen Planus, Oral ; diagnosis ; pathology ; therapy ; Phototherapy ; Prednisone ; therapeutic use ; Recombinant Fusion Proteins ; therapeutic use

OBJECTIVETo observe the effect of hTFF1 fusion protein on gastric mucosal lesion in mice after burn injury.

METHODSThe pET32alpha-hTFF1 vector were transfected into E.coli Origami B (DE3), and rhTFF1 fusion protein was expressed by IPTG induction. Mice were inflicted with 30% TBSA full-thickness burn, then were divided into burn treatment (BT, with treatment of rhTEF1 fusion protein by gavage), burn control (BC, with treatment of isotonic saline by gavage), and normal control (NC) groups according to block randomized design. Gastric mucosal lesion, including appearance of gastric mucosa, injury index, pathological change, were compared between BT and BC groups before and after burn injury, and above indices in NC group were also examined.

RESULTSThe rhTFF1 fusion protein was expressed with good specificity confirmed with Western blot analysis. The gastric erosion rate was 77.8% and 22.2% respectively in BC and T group. The injury index was 6.2 +/- 2.0 and 2.0 +/- 1.2 respectively in BC and T group. Above indices in C group were 0.

CONCLUSIONThe rhTFF1 fusion protein can be expressed in E.coli expression systems, which can obviously ameliorate gastric mucosal lesion in mice after burn injury.

Animals ; Burns ; pathology ; therapy ; Disease Models, Animal ; Gastric Mucosa ; pathology ; Humans ; Mice ; Recombinant Fusion Proteins ; therapeutic use ; Trefoil Factor-1 ; Tumor Suppressor Proteins ; therapeutic use ; Wound Healing

SARS-CoV-2-induced immune thrombocytopenia (SARS-CoV-2-induced ITP) is an autoimmune disease secondary to virus infections. Its diagnosis is often based on exclusion of other possible causes of thrombocytopenia in COVID-19 patients. Common laboratory examinations include coagulation function, thrombopoietin and drug-dependent antibodies. Since both bleeding and thrombosis risks are seen in SARS-CoV-2-induced ITP patients, individual remedy is essential for the treatment of this disease. Because thrombopoietin receptor agonist(TPO-RA) has the side effect of accelerating thrombosis and may aggravate the pulmonary embolism symptoms of patients, it should be used for refractory SARS-CoV-2-induced ITP patients only. This review briefly summarizes the recent research progress in the pathogenesis, diagnosis and treatment of SARS-CoV-2-induced ITP.
Humans ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; SARS-CoV-2 ; COVID-19/complications* ; Thrombocytopenia ; Thrombosis/drug therapy* ; Thrombopoietin/therapeutic use* ; Recombinant Fusion Proteins/therapeutic use*

OBJECTIVE: To observe the effect of cyclosporine and simulect mono or combination therapy on cardiac allo-transplantation in rats. METHODS: Recipients with allografts were treated with different doses of cyclosporine and/or simulect after cardiac allo-transplantation. Graft survival time was observed; the histopathological examination of graft tissues was performed; and levels of serum IL-2 and IL-4 were determined. RESULTS: Mono or combination therapy with cyclosporine and/or simulect increased the survival of cardiac allografts. With the prolongation of survival time of the grafts, the rejection of grafts was moderated. The serum IL-2 level increased in acute rejected grafts; the serum IL-4 level increased evidently in long survival grafts. CONCLUSION Cyclosporine and simulect have an effect in the prolongation of cardiac allograft survival in rats, and the combination therapy shows an evident synergistic effect.
Animals ; Antibodies, Monoclonal ; pharmacology ; therapeutic use ; Basiliximab ; Combined Modality Therapy ; Cyclosporine ; pharmacology ; therapeutic use ; Female ; Graft Rejection ; immunology ; Heart Transplantation ; adverse effects ; Immunosuppressive Agents ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Recombinant Fusion Proteins ; pharmacology ; therapeutic use

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease of the central nervous system (CNS); it serves as a model for the human multiple sclerosis (MS). In mice, EAE is mediated by T cells specific for various myelin basic proteins which migrate from the periphery to the CNS. In search of a way to prevent the induction and progression of EAE, we observed the effects of recombinant immunotoxin IP10-DT390 on blocking or eliminating the active T cells in the EAE model. In this paper is presented an experimental gene therapy-based model in which the mice were made resistant to EAE induction by plasmid DNA encoding recombinant immunotoxin that was injected into the leg muscles of mice. The new immuno-biological construct could selectively impair autoreactive T-cell homing while the duration of clinical signs is shorter, and the new construct would not affect other components of the immune response. These data demonstrated the effectiveness of the constructs in the treatment of EAE and suggested its usefulness in the treatment of other autoimmune diseases.
Animals ; Chemokine CXCL10 ; biosynthesis ; genetics ; therapeutic use ; Diphtheria Toxin ; biosynthesis ; genetics ; therapeutic use ; Encephalomyelitis, Autoimmune, Experimental ; immunology ; pathology ; therapy ; Female ; Genetic Therapy ; Immunoglobulin Fragments ; biosynthesis ; genetics ; therapeutic use ; Immunotoxins ; genetics ; metabolism ; therapeutic use ; Mice ; Mice, Inbred C57BL ; Receptors, CXCR3 ; metabolism ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; therapeutic use ; Recombinant Proteins ; biosynthesis ; genetics ; therapeutic use ; T-Lymphocytes ; immunology ; Transfection

Heat shock protein gp96 isolated from tumor tissues holds great promise for tumor immunotherapy. However, at present only very limited amount of gp96 protein can be isolated from tumor tissues. Here, we reconstituted the yeast-expressed gp96 (recombinant gp96, rgp96) with B16.F10 melanoma antigens in vitro to prepare new gp96 tumor vaccine on large-scale, and analyzed its induction of specific anti-tumor immunoresponses by ELISPOT, IFN-gamma intracellular staining and cytotoxicity assays. Immunization with rgp96-tumor antigen complexes significantly inhibited B16 tumor growth compared with either rgp96 or tumor antigens alone and led to enhancement of tumor-specific T-cell activities, which was found similar to that of tumor tissue derived gp96. Our results therefore may provide bases for large-scale preparation of the new generation of gp96 tumor vaccines.
Animals ; Cancer Vaccines ; biosynthesis ; genetics ; immunology ; therapeutic use ; Female ; Heat-Shock Proteins ; biosynthesis ; genetics ; immunology ; therapeutic use ; Melanoma, Experimental ; therapy ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; immunology ; therapeutic use ; Skin Neoplasms ; therapy ; Yeasts ; genetics ; metabolism

OBJECTIVETo investigate the inhibitory effects of humanized monoclonal antibody-3 (huTNT-3) mediated truncated tissue factor (tTF) on the H(22) hepatoma-bearing mice, and to explore its mechanisms.

METHODSThe coagulation activity of the huTNT-3/tTF fusion protein was detected by clotting assay and clotting factor X (FX) activation test in vitro. Mouse hepatoma cell line H(22) cells were inoculated subcutaneously into mice to establish the mouse models of hepatoma. The mice were randomly divided into two groups to be injected once with huTNT-3/tTF fusion protein or tTF protein labeled with rhodamine B isothiocyanate (RBITC), respectively. The localization of huTNT-3/tTF fusion protein in the mouse hepatoma tissue was analyzed by confocal laser scanning microscopy 24 hour after the injection. Fifteen mice were randomly divided into three groups to be injected with the huTNT-3/tTF fusion protein, tTF protein or phosphate buffered saline (PBS) once, respectively. The tumor size was measured every two days to calculate the tumor volume. Ten days after the injection the mice were sacrificed. Samples of the tumor, heart, livers, spleen, lung, kidney and brains of the mice were taken for histopathological examination.

RESULTSBoth the huTNT-3/tTF fusion protein and tTF protein effectively promoted blood coagulation. Under the conditions of Ca(2+), the coagulation time in the 1.5, 3, 6 µmol/L huTNT-3/tTF groups was (12.90 ± 0.60) min, (10.39 ± 0.40) min and(8.15 ± 0.24) min, respectively, and the coagulation time of the 1.5, 3, 6 µmol/L tTF groups was (14.23 ± 0.46) min, (12.10 ± 0.49) min and (9.83 ± 0.52) min, respectively, the difference between the two groups was not significant (F = 0.145, P = 0.705). The huTNT-3/tTF fusion protein was similar to the tTF protein in the ability of activating FX (t = 0.101, P > 0.05). The confocal laser scanning microscopic analysis showed that RBITC-fluorescence labeled huTNT-3/tTF fusion protein was enriched in the hepatoma tissue. The tumor volume of the huTNT-3/tTF fusion protein group was significantly lower than that of the tTF and PBS groups (both P < 0.001), however, there was not significant difference between the tTF and PBS groups (t = -0.616, P > 0.05). The survival time of the huTNT-3/tTF group was (25.5 ± 2.5) d, significantly longer than that of the PBS group (17.3 ± 1.9) d and the tTF group (18.6 ± 1.9) d, (both P < 0.05).

CONCLUSIONThe huTNT-3/tTF fusion protein retains the coagulation ability and has the capability of targeting to tumor vasculature, and induces thrombosis in the tumor vessels, thus to suppress the growth of hepatoma in the mice.

Animals ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Blood Coagulation ; Carcinoma, Hepatocellular ; blood ; pathology ; therapy ; Cell Line, Tumor ; Factor X ; metabolism ; Liver Neoplasms ; blood ; pathology ; therapy ; Male ; Mice ; Neoplasm Transplantation ; Random Allocation ; Recombinant Fusion Proteins ; therapeutic use ; Thromboplastin ; therapeutic use ; Tumor Burden

BACKGROUNDLong-term use of steroid with large dosage might cause many adverse effects in kidney transplant patients; reducing steroid dosage to a low level for maintenance is helpful in avoiding the side-effects, but meanwhile, acute rejection may rise to be a main concern. The present research monitored the immune function changes and the incidence of acute rejection and infection after rapid steroid reduction to investigate the safety of this strategy.

METHODSA prospective trial was conducted, using tacrolimus and mycophenolate mofetil as the basic immunosuppressive regimen, in addition to antibody induction with basiliximab. Corticosteroid dosage was rapidly reduced to 10 mg/d seven days post-transplantation in the experimental group, and the standard corticosteroid therapy was employed in the control group. Patient immunity was monitored by the Immune Cell Function Assay pre- and two weeks post-transplantation. The incidence of acute rejection and infection were compared between the experimental and control group.

RESULTSComparison of intracellular adenosine triphosphate (iATP) values detected two weeks post-transplantation for the control group ((324 ± 45) ng/ml) and the experimental group ((345 ± 91) ng/ml) did not reveal a significant difference (P > 0.05). The incidence of acute rejection was analogous between groups (P > 0.05), while an increased incidence of infection was observed in the control group (53% (n = 16)) versus the experimental group (22% (n = 6), P < 0.05). Overall, recipients in the control group had longer and more recurrent infections than those in the experimental group (P < 0.05). Patients in the control group had a lower immune response ((235 ± 35) ng/ml) than those in the experimental group ((286 ± 16) ng/ml) when infection occurred (P < 0.05).

CONCLUSIONRapid reduction of steroid early after kidney transplantation does not lead to a significant rise in patient immunity. It is a safe and effective therapy for kidney transplant patients.

Adolescent ; Adrenal Cortex Hormones ; metabolism ; Adult ; Antibodies, Monoclonal ; therapeutic use ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; immunology ; Male ; Middle Aged ; Prospective Studies ; Recombinant Fusion Proteins ; therapeutic use ; Young Adult