transforming-growth-factor-beta and Hemolysis

Transcatheter arterial embolization (TAE) is one of the first-line treatments for advanced hepatocellular cancer. The pain caused by TAE is a stark complication, which remains to be prevented by biomedical engineering methods.. In summary, CB/Lid-10 has relatively good biocompatibility and bioactivity, and it can serve as a promising candidate for painless transcatheter arterial embolization.

Topics: Carrageenan; Embolization, Therapeutic; Hemolysis; Humans; Inflammation; Interleukin-10; Interleukin-6; Lidocaine; Transforming Growth Factor beta

We describe a novel bioflocculant, MBF-15, which is an exopolysaccharide extracted from the alkaliphilic bacterium Paenibacillus jamilae. The biophysical characteristics of MBF-15 were determined using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. MBF-15 was also evaluated for its biocompatibility by examining its inflammatory, coagulant, and hemostatic properties in vitro and in vivo. Pretreatment of peripheral blood mononuclear cells with MBF-15 inhibited lipopolysaccharide-stimulated expression of inducible nitric oxide synthase, production of nitric oxide, and secretion of pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-6. In addition, MBF-15 increased both mRNA and protein levels of the anti-inflammatory cytokines transforming growth factor-β and IL-10. The hemocompatibility of MBF-15 was investigated by measuring the hemolysis ratio and clotting times. MBF-15 had high pro-thrombogenic activity but was not hemolytic. In a rat model, MBF-15 showed superior hemostatic properties compared with chitosan. Thus, MBF-15 offers a promising combination of anti-inflammatory and pro-coagulant properties that may be useful for hemostasis in a variety of clinical settings.

Topics: Animals; Anti-Inflammatory Agents; Cells, Cultured; Coagulants; Flocculation; Gene Expression; Hemolysis; Interleukin-10; Leukocytes, Mononuclear; Lipopolysaccharides; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Paenibacillus; Rats; Transforming Growth Factor beta

Iron is the most abundant metal in mammalian cells, and plays a pivotal role in many metabolic processes. Dysregulated iron homeostasis is involved in the cause of a number of pathological processes including renal diseases.. Longitudinal MRI scans of salt-loaded spontaneously hypertensive stroke-prone rats (SHRSP), an animal model that spontaneously develops hypertensive nephropathy, showed a decrease in renal and hepatic T2 SI (a sign of iron accumulation) of, respectively, 42.3 ± 2.5% (P < 0.01) and 60.4 ± 15.1% (P < 0.01) in comparison with SHRSP fed a standard diet. This was accompanied by the development of renal inflammation and oxidative stress (as evaluated by immunohistochemical and proteomic analyses), mitochondrial dysfunction, massive proteinuria and sustained intravascular hemolysis with the subsequent depletion of plasma haptoglobin, which was responsible for the renal uptake of hemoglobin and iron accumulation. In order to investigate the role of iron in these pathological processes, we subcutaneously treated the salt-loaded rats with the iron chelator deferoxamine (200 mg/kg per day). The pharmacological treatment prevented iron tissue accumulation, as indicated by the increase in renal and hepatic T2 SI of, respectively, 120.0 ± 10.1% (P < 0.01) and 73.9 ± 4.4% (P < 0.01) in comparison with salt-loaded rats treated with vehicle alone. Deferoxamine also preserved renal morphology and function, the renal infiltration of ED-1-positive macrophages/monocytes, and the expression of MCP-1 and TGF-β mRNA, reduced the level of reactive oxygen species, and improved the activity of mitochondrial cytochrome c oxidase.. These findings suggest that iron dysmetabolism is involved in the development of hypertensive nephropathy in SHRSP.

Topics: Animals; Blood Pressure; Deferoxamine; Disease Models, Animal; Hemolysis; Homeostasis; Hypertension, Renal; Iron; Kidney; Male; Models, Animal; Nephritis; Oxidative Stress; Proteinuria; Proteomics; Rats; Rats, Inbred SHR; Reactive Oxygen Species; Sodium Chloride, Dietary; Stroke; Transforming Growth Factor beta

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a critical regulator of osteogenic capacity that is commonly used in bone grafts. The effectiveness of rhBMP-2 may be reduced as it can become unstable and degraded after injection into the body. Microspheres are considered appropriate vehicles for the sustained release of proteins in vivo. In this study, rhBMP-2 microspheres were manufactured using the water-in-oil-in-water (W/O/W) double-emulsion solvent-extraction technique by encapsulation in poly(lactic-co-glycolic) acid (PLGA). The microspheres were then embedded in two hydrogels made of either poloxamer 407 hydrogel or chitosan thioglycolic acid (CS-TA). The encapsulation efficiency and in vitro release of rhBMP-2 were examined and compared with the control release system (rhBMP-2 microspheres alone). The rhBMP-2 microspheres in the CS-TA hydrogel showed the lowest burst release (about 40% in the first 8h) among the three groups. The mechanisms may be the high viscosity of CS-TA hydrogel and the sustained release characteristics of CS-TA itself. The CS-TA hydrogel combined with PLGA microspheres can efficiently encapsulate rhBMP-2, control the burst release at early time points, and provide sustained release in vitro. It may be an appropriate rhBMP-2 vehicle for bone regeneration.

Topics: Animals; Bone Morphogenetic Protein 2; Chitosan; Delayed-Action Preparations; Drug Compounding; Drug Delivery Systems; Enzyme-Linked Immunosorbent Assay; Erythrocytes; Hemolysis; Hydrogels; In Vitro Techniques; Kinetics; Microscopy, Electron, Scanning; Microspheres; Particle Size; Rabbits; Recombinant Proteins; Solubility; Temperature; Thioglycolates; Transforming Growth Factor beta; Viscosity

In many hemolytic disorders, such as malaria, the release of free heme has been involved in the triggering of oxidative stress and tissue damage. Patients presenting with severe forms of malaria commonly have impaired regulatory responses. Although intriguing, there is scarce data about the involvement of heme on the regulation of immune responses. In this study, we investigated the relation of free heme and the suppression of anti-inflammatory mediators such as PGE(2) and TGF-beta in human vivax malaria. Patients with severe disease presented higher hemolysis and higher plasma concentrations of Cu/Zn superoxide dismutase (SOD-1) and lower concentrations of PGE(2) and TGF-beta than those with mild disease. In addition, there was a positive correlation between SOD-1 concentrations and plasma levels of TNF-alpha. During antimalaria treatment, the concentrations of plasma SOD-1 reduced whereas PGE(2) and TGF-beta increased in the individuals severely ill. Using an in vitro model with human mononuclear cells, we demonstrated that the heme effect on the impairment of the production of PGE(2) and TGF-beta partially involves heme binding to CD14 and depends on the production of SOD-1. Aside from furthering the current knowledge about the pathogenesis of vivax malaria, the present results may represent a general mechanism for hemolytic diseases and could be useful for future studies of therapeutic approaches.

Topics: Adolescent; Adult; Cells, Cultured; Dinoprostone; Enzyme-Linked Immunosorbent Assay; Erythrocytes; Female; Flow Cytometry; Heme; Hemolysis; Humans; Inflammation; Leukocytes, Mononuclear; Lipopolysaccharide Receptors; Malaria, Vivax; Male; Middle Aged; Plasmodium vivax; RNA Interference; Superoxide Dismutase; Transforming Growth Factor beta; Young Adult

Cutaneous leg ulcers are common in sickle cell anaemia and their risk might be genetically determined. Sickle cell anaemia patients were studied to examine the relationship of leg ulcers with haemolysis and with single nucleotide polymorphisms (SNPs) in candidate genes that could affect sickle vasoocclusion. Leg ulcer patients had lower haemoglobin levels and higher levels of lactate dehydrogenase, bilirubin, aspartate transaminase and reticulocytes than did control patients with sickle cell anaemia but without leg ulcers. Age-adjusted comparisons showed that sickle cell anaemia-alpha thalassaemia was more frequent among controls than cases. These results strongly suggested that the likelihood of having leg ulcers was related to the intensity of haemolysis. 215 SNPs in more than 100 candidate genes were studied. Associations were found with SNPs in Klotho, TEK and several genes in the TGF-beta/BMP signalling pathway by genotypic association analyses. KL directly or indirectly promotes endothelial nitric oxide (NO) production and the TEK receptor tyrosine kinase is involved in angiogenesis. The TGF-beta/BMP signalling pathway modulates wound healing and angiogenesis, among its other functions. Haemolysis-driven phenotypes, such as leg ulcers, could be improved by agents that reduce sickle erythrocyte density or increase NO bioavailability.

Topics: Adult; Anemia, Sickle Cell; Bone Morphogenetic Proteins; Female; Genotype; Glucuronidase; Hemolysis; Humans; Klotho Proteins; Leg Ulcer; Male; Phenotype; Polymorphism, Single Nucleotide; Receptor, TIE-2; Thalassemia; Transforming Growth Factor beta

In periodontal disease, interleukin-1beta (IL-1beta) is responsible for the matrix breakdown through excessive production of degrading enzymes by periodontal ligament fibroblasts and osteoblasts. Transforming growth factor-beta (TGF-beta) plays an important role in tissue regeneration as one of the factors capable of counteracting IL-1beta effects. In this study, we investigated the in vitro effect of avocado and soya unsaponifiables (ASU) on the expression of TGF-beta1, TGF-beta2, and bone morphogenetic protein-2 (BMP-2) by human periodontal ligament (HPL) and human alveolar bone (HAB) cells in the presence of IL-1beta.. HPL and HAB cells were incubated for 48 hours with ASU (10 microg/ml) in the presence or absence of IL-1beta (10 ng/ml). The steady-state levels of TGF-beta1, TGF-beta2, and BMP-2 mRNAs were determined by Northern blot or reverse transcription-polymerase chain reaction (RT-PCR). The amounts of TGF-beta1 and TGF-beta2 proteins were measured by enzyme-linked immunosorbent assay (ELISA).. The data indicated that IL-1beta strongly decreases the expression of TGF-beta1 and TGF-beta2 by HPL cells. ASU were capable of opposing the cytokine effect. In HAB cells, TGF-beta1 and BMP-2 mRNA levels were downregulated by the cytokine. ASU were found to reverse the IL-1beta-inhibiting effect. In contrast, the cytokine stimulated the production of TGF-beta2 in alveolar bone cells, with no significant effect of ASU.. The results indicate that the IL-1beta-driven erosive effect in periodontitis could be enhanced by a decreased expression of members of the TGF-beta family. The ASU stimulation of TGF-beta1, TGF-beta2, and BMP-2 expression may explain their promoting effects in the treatment of periodontal disorders, at least partly. These findings support the hypothesis that ASU could exert a preventive action on the deleterious effects exerted by IL-1beta in periodontal diseases.

Topics: Adolescent; Adult; Alveolar Process; Bone Morphogenetic Protein 2; Bone Morphogenetic Proteins; Cells, Cultured; Female; Fibroblasts; Hemolysis; Humans; Inflammation Mediators; Interleukin-1; Male; Periodontal Ligament; Persea; Plant Oils; Soybean Oil; Sterols; Transforming Growth Factor beta; Up-Regulation