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| dc.creator | Oliveira, Gabriel Ferreira | |
| dc.date.accessioned | 2025-08-22T12:13:00Z | |
| dc.date.available | 2027-08-03 | |
| dc.date.available | 2025-08-22T12:13:00Z | |
| dc.date.issued | 2025-07-03 | |
| dc.identifier.citation | OLIVEIRA, Gabriel Ferreira. Avaliação dos Mediadores inflamatórios e microbioma no exsudato de feridas de pacientes com úlcera. Orientador: Vitor Fortuna; Coorientador: Roberto José Meyer Nascimento. 2025. 105 f. Dissertação (Mestrado em Imunologia) - Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador (BA), 2025. | pt_BR |
| dc.identifier.uri | https://repositorio.ufba.br/handle/ri/42768 | |
| dc.description.abstract | Introduction: Leg ulcers in sickle cell disease (SCDLU) represent debilitating and chronic manifestations associated with disease severity, resulting in delayed wound healing and unpredictable recurrence linked to aberrant regulation of inflammatory mediators. Although elevated levels of cytokines and altered microbiome composition have been associated with impaired healing in other wound types, their specific role in SCDLU remains incompletely understood. Objective: To characterize the exudate profile of SCDLU, with particular emphasis on inflammatory mediator analysis and identification of lesion associated microbiome. Methods: Wound exudate samples were collected between January 2023 and June 2024 at the outpatient clinics of Professor Edgard Santos University Hospital (HUPES) and the State Reference Center for Sickle Cell Disease (CERPDF-RV/Hemoba) (CAAE: 56643222.0.0000.5662). This cross-sectional study analyzed clinical data, inflammatory profiles, and wound microbiome composition. Cytokines were quantified using sandwich ELISA (R&D Systems; Invitrogen), and statistical analyses were performed using GraphPad Prism (version 9). Results: The study included 40 SCD patients, comprising 63 analyzed ulcers. Median age was 41 years, with 55.0% male participants. Each patient was presented with 1-4 cutaneous lesions and laboratory data revealed chronic hemolysis and anemia. IL-6, PSGL-1, and P-selectin levels were significantly lower in ulcers with small diameter, while IFN-γ and IL-8 showed no significant differences between groups. ROC analysis indicated that IL-6, PSGL-1, and P-selectin effectively discriminated against lesion size, suggesting their potential as inflammatory biomarkers. Furthermore, larger ulcers exhibited greater bacterial diversity in microbiome analysis. Conclusion: Our findings demonstrate that IL-6, PSGL-1, and P-selectin play significant roles in SCDLU pathophysiology and may serve as reliable biomarkers for lesion size. The observed increase in bacterial diversity in extensive ulcers suggests potential microbiome involvement in perpetuating local inflammation. These results may contribute to improved clinical assessment and therapeutic management of SCD-associated ulcers. | pt_BR |
| dc.description.sponsorship | Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB) | pt_BR |
| dc.language | por | pt_BR |
| dc.publisher | Universidade Federal da Bahia | pt_BR |
| dc.rights | Acesso Restrito/Embargado | pt_BR |
| dc.subject | Úlcera falciforme | pt_BR |
| dc.subject | Anemia Falciforme | pt_BR |
| dc.subject | Inflamação | pt_BR |
| dc.subject | Cicatrização | pt_BR |
| dc.subject | Biomarcador | pt_BR |
| dc.subject.other | Sickle cell leg ulcer | pt_BR |
| dc.subject.other | Inflammation | pt_BR |
| dc.subject.other | Anemia, Sickle Cell | pt_BR |
| dc.subject.other | Healing | pt_BR |
| dc.subject.other | Biomarker | pt_BR |
| dc.title | Avaliação dos mediadores inflamatórios e microbioma no exsudato de feridas de pacientes com úlcera falciforme | pt_BR |
| dc.title.alternative | Evaluation of inflammatory mediators and the microbiome in wound exudate from patients with sickle cell ulcers | pt_BR |
| dc.type | Dissertação | pt_BR |
| dc.publisher.program | Programa de Pós-Graduação em Imunologia - (PPGIM) | pt_BR |
| dc.publisher.initials | UFBA | pt_BR |
| dc.publisher.country | Brasil | pt_BR |
| dc.subject.cnpq | CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA::IMUNOLOGIA APLICADA | pt_BR |
| dc.contributor.advisor1 | Fortuna, Vitor Antônio | |
| dc.contributor.advisor1ID | https://orcid.org/0000-0001-7281-3287 | pt_BR |
| dc.contributor.advisor1Lattes | http://lattes.cnpq.br/3535550424970530 | pt_BR |
| dc.contributor.advisor-co1 | Nascimento, Roberto José Meyer | |
| dc.contributor.advisor-co1ID | https://orcid.org/0000-0002-4727-4805 | pt_BR |
| dc.contributor.advisor-co1Lattes | http://lattes.cnpq.br/9574426480028427 | pt_BR |
| dc.contributor.referee1 | Aleluia, Milena Magalhães | |
| dc.contributor.referee1ID | https://orcid.org/0000-0001-6928-824X | pt_BR |
| dc.contributor.referee1Lattes | http://lattes.cnpq.br/4312312024270025 | pt_BR |
| dc.contributor.referee2 | Cordeiro, Soraia Machado | |
| dc.contributor.referee2ID | https://orcid.org/0000-0001-5320-892X | pt_BR |
| dc.contributor.referee2Lattes | http://lattes.cnpq.br/9277624701608674 | pt_BR |
| dc.contributor.referee3 | Fortuna, Vitor Antônio | |
| dc.contributor.referee3ID | https://orcid.org/0000-0001-7281-3287 | pt_BR |
| dc.contributor.referee3Lattes | http://lattes.cnpq.br/3535550424970530 | pt_BR |
| dc.creator.ID | https://orcid.org/0009-0008-1163-1402 | pt_BR |
| dc.creator.Lattes | https://lattes.cnpq.br/9844466316389564 | pt_BR |
| dc.description.resumo | Introdução: Úlceras em membros inferiores na doença falciforme (DF) são manifestações debilitantes e crônicas associadas à gravidade patológica que resultam em cicatrização tardia e recorrência imprevisível associadas à desregulação de mediadores inflamatórios e hemolíticos. Embora altos níveis dos mediadores inflamatórios e microbioma tenham sido relacionados à cicatrização prejudicada em outras lesões, seu papel específico em úlceras de DF ainda não está totalmente esclarecido. Objetivo: Caracterizar os aspectos do exsudato de úlceras falciformes, com ênfase na análise de mediadores inflamatórios e na identificação do microbioma associado às lesões. Metodologia: Foram coletadas amostras de exsudato de feridas entre janeiro de 2023 e junho de 2024 no ambulatório do Hospital Universitário Professor Edgard Santos (HUPES) e no Centro Estadual de Referência à Pessoa com Doença Falciforme (CERPDF-RV/Hemoba) (CAAE: 56643222.0.0000.5662). O estudo, de delineamento transversal, analisou dados clínicos, perfil inflamatório e composição do microbioma das lesões. As citocinas foram quantificadas por ELISA sanduíche (R&D Systems; Invitrogen), e as análises estatísticas foram realizadas no GraphPad Prism (versão 9). Resultados: 40 pacientes incluídos com doença falciforme, totalizando 63 úlceras analisadas. A mediana de idade foi de 41 anos, com 55,0% sendo do sexo masculino. Cada paciente apresentou de 1 a 4 lesões cutâneas e exames laboratoriais indicaram hemólise e anemia crônica. Níveis de IL-6, PSGL-1 e P-selectina foram significativamente menores em úlceras de menor dimensão, enquanto o IFN-γ e IL-8 não diferiu entre os grupos avaliados. A análise ROC indicou que IL-6, PSGL-1 e P-selectina discriminaram bem o tamanho das lesões, sugerindo seu potencial como biomarcadores inflamatórios. Além disso, úlceras maiores apresentaram maior diversidade bacteriana no microbioma. Conclusão: Os resultados indicam que IL-6, PSGL-1 e P-selectina desempenham um papel relevante na fisiopatologia das úlceras em pacientes com DF, podendo servir como biomarcadores associados ao tamanho das lesões. Além disso, a maior diversidade bacteriana em úlceras extensas sugere uma possível influência do microbioma na perpetuação da inflamação local. Esses achados podem auxiliar na avaliação clínica e no tratamento dessas lesões. | pt_BR |
| dc.publisher.department | Instituto de Ciências da Saúde - ICS | pt_BR |
| dc.relation.references | Prefeitura do Município de São Paulo. Secretaria Municipal da Saúde. Manual de padronização de curativos. São Paulo: Secretaria Municipal da Saúde, 2021. ABDUL-HUSSEIN, H. K.; AL-MAMMORI, H. S.; HASSAN, M. K. Evaluation of the expression of red blood cell CD36, interleukin-6 and interleukin-8 in sickle cell anemia pediatric patients. Cytokine, [s. l.], v. 143, p. 155534, 2021. AL GHAZAL, P. et al. Evaluation of the Essen Rotary as a new technique for bacterial swabs: results of a prospective controlled clinical investigation in 50 patients with chronic leg ulcers. International Wound Journal, [s. l.], v. 11, n. 1, p. 44–49, 2014. ALDALLAL, S. M. Mini review: leg ulcers - a secondary complication of sickle cell disease. International Journal of General Medicine, [s. l.], v. 12, p. 279–282, 2019. ALLISON, A. C. Protection Afforded by Sickle-cell Trait Against Subtertian Malarial Infection. British Medical Journal, [s. l.], v. 1, n. 4857, p. 290–294, 1954. ALMAGRO-MOLTO, M.; EDER, W.; SCHUBERT, S. Bordetella trematum in chronic ulcers: report on two cases and review of the literature. Infection, [s. l.], v. 43, n. 4, p. 489–494, 2015. ALOUI, C. et al. The Signaling Role of CD40 Ligand in Platelet Biology and in Platelet Component Transfusion. International Journal of Molecular Sciences, [s. l.], v. 15, n. 12, p. 22342–22364, 2014. ALTMAN, I. A. et al. A treatment algorithm to identify therapeutic approaches for leg ulcers in patients with sickle cell disease. International Wound Journal, [s. l.], v. 13, n. 6, p. 1315–1324, 2016. ANTWI-BOASIAKO, C. et al. A study of the geographic distribution and associated risk factors of leg ulcers within an international cohort of sickle cell disease patients: the CASiRe group analysis. Annals of Hematology, [s. l.], v. 99, n. 9, p. 2073–2079, 2020. ASHCROFT, G. S. et al. TNFα is a therapeutic target for impaired cutaneous wound healing. Wound Repair and Regeneration, [s. l.], v. 20, n. 1, p. 38–49, 2012a. ASHCROFT, G. S. et al. Tumor necrosis factor-alpha (TNF-α) is a therapeutic target for impaired cutaneous wound healing. Wound Repair and Regeneration, [s. l.], v. 20, n. 1, p. 38–49, 2012b. ATARASHI, K. et al. Rolling of Th1 cells via P-selectin glycoprotein ligand-1 stimulates LFA-1-mediated cell binding to ICAM=1. Journal of Immunology, [s. l.], v. 174, n. 3, p. 1424–1432, 2005. AYOOLA, O. O. et al. Intima-media thickness of the common femoral artery as a marker of leg ulceration in sickle cell disease patients. Blood Advances, [s. l.], v. 2, n. 22, p. 90 3112–3117, 2018. AZBELL, R. C. G.; DESAI, P. C. Treatment dilemmas: strategies for priapism, chronic leg ulcer disease, and pulmonary hypertension in sickle cell disease. Hematology. American Society of Hematology. Education Program, [s. l.], v. 2021, n. 1, p. 411–417, 2021. BABALOLA, O. A. et al. Haematological indices of sickle cell patients with chronic leg ulcers on compression therapy. African Journal of Laboratory Medicine, [s. l.], v. 9, n. 1, p. 1037, 2020a. BABALOLA, O. A. et al. Haematological indices of sickle cell patients with chronic leg ulcers on compression therapy. African Journal of Laboratory Medicine, [s. l.], v. 9, n. 1, 2020b. Disponível em: http://www.ajlmonline.org/index.php/AJLM/article/view/1037. Acesso em: 27 abr. 2025. BALLAS, S. K.; MOHANDAS, N. Pathophysiology of vaso-occlusion. Hematology/Oncology Clinics of North America, [s. l.], v. 10, n. 6, p. 1221–1239, 1996. BELCHER, J. D. et al. The BACH1 inhibitor ASP8731 inhibits inflammation and vaso-occlusion and induces fetal hemoglobin in sickle cell disease. Frontiers in Medicine, [s. l.], v. 10, 2023. Disponível em: https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1101501/full. Acesso em: 8 out. 2024. BELISÁRIO, A. R. et al. Association between inflammatory molecules, nitric oxide metabolites and leg ulcers in individuals with sickle cell anemia. Hematology, Transfusion and Cell Therapy, [s. l.], v. 44, n. 2, p. 169–176, 2022. BERGANT SUHODOLČAN, A.; LUZAR, B.; KECELJ LESKOVEC, N. Matrix metalloproteinase (MMP)-1 and MMP-2, but not COX-2 serve as additional predictors for chronic venous ulcer healing. Wound Repair and Regeneration, [s. l.], v. 29, n. 5, p. 725–731, 2021. BILLETT, H. H.; PATEL, Y.; RIVERS, S. P. Venous insufficiency is not the cause of leg ulcers in sickle cell disease. American Journal of Hematology, [s. l.], v. 37, n. 2, p. 133–134, 1991. BISWAL, S. et al. Oxidative stress, antioxidant capacity, biomolecule damage, and inflammation symptoms of sickle cell disease in children. Hematology, [s. l.], v. 24, n. 1, p. 1–9, 2019. BLOCK, H.; ROSSAINT, J.; ZARBOCK, A. The Fatal Circle of NETs and NET-Associated DAMPs Contributing to Organ Dysfunction. Cells, [s. l.], v. 11, n. 12, p. 1919, 2022. BOOTHBY, I. C.; COHEN, J. N.; ROSENBLUM, M. D. Regulatory T cells in Skin Injury: At the Crossroads of Tolerance and Tissue Repair. Science immunology, [s. l.], v. 5, n. 47, p. eaaz9631, 2020a. BOOTHBY, I. C.; COHEN, J. N.; ROSENBLUM, M. D. Regulatory T cells in Skin Injury: At the Crossroads of Tolerance and Tissue Repair. Science immunology, [s. l.], v. 5, n. 47, p. eaaz9631, 2020b. 91 BOWERS, A. S. et al. Blood Viscosity and the Expression of Inflammatory and Adhesion Markers in Homozygous Sickle Cell Disease Subjects with Chronic Leg Ulcers. PLOS ONE, [s. l.], v. 8, n. 7, p. e68929, 2013. BOWERS, A. S.; PEPPLE, D. J.; REID, H. L. Optimal haematocrit in subjects with normal haemoglobin genotype (HbAA), sickle cell trait (HbAS), and homozygous sickle cell disease (HbSS). Clinical Hemorheology and Microcirculation, [s. l.], v. 47, n. 4, p. 253–260, 2011. BRANCATO, S. K.; ALBINA, J. E. Wound Macrophages as Key Regulators of Repair: Origin, Phenotype, and Function. The American Journal of Pathology, [s. l.], v. 178, n. 1, p. 19–25, 2011. BRITO, L. S. et al. DA SUPERPROTEÇÃO AO ESTIGMA: RELAÇÕES FAMILIARES DE PESSOAS COM ÚLCERA DE PERNA E DOENÇA FALCIFORME. Revista Baiana de Enfermagem , [s. l.], v. 35, 2021. Disponível em: https://periodicos.ufba.br/index.php/enfermagem/article/view/37793. Acesso em: 15 ago. 2024. BRUNI, E. et al. The healing process of diabetic ulcers correlates with changes in the cutaneous microbiota. Scientific Reports, [s. l.], v. 14, p. 27628, 2024. BUECHLER, C. et al. Detection and Characterization of Clinical Bordetella trematum Isolates from Chronic Wounds. Pathogens, [s. l.], v. 10, n. 8, p. 966, 2021. BURIAN, E. A. et al. A simplified method for monitoring cytokines in wound fluid. Wound Repair and Regeneration: Official Publication of the Wound Healing Society [and] the European Tissue Repair Society, [s. l.], v. 31, n. 1, p. 47–55, 2023. BURIAN, E. A. et al. Cytokines and Venous Leg Ulcer Healing—A Systematic Review. International Journal of Molecular Sciences, [s. l.], v. 23, n. 12, p. 6526, 2022. BYEON, J. et al. Insights into the skin microbiome of sickle cell disease leg ulcers. Wound Repair and Regeneration: Official Publication of the Wound Healing Society [and] the European Tissue Repair Society, [s. l.], v. 29, n. 5, p. 801–809, 2021. CACKOVIC, M. et al. Leg Ulceration in the Sickle Cell Patient. Journal of the American College of Surgeons, [s. l.], v. 187, n. 3, p. 307, 1998. CANÇADO, R. D. et al. Estimated mortality rates of individuals with sickle cell disease in Brazil: real-world evidence. Blood Advances, [s. l.], v. 7, n. 15, p. 3783–3792, 2023. CARVALHO, M. O. S. et al. Inflammatory mediators in sickle cell anaemia highlight the difference between steady state and crisis in paediatric patients. British Journal of Haematology, [s. l.], v. 182, n. 6, p. 933–936, 2018. CATELLA, J. et al. Controversies in the pathophysiology of leg ulcers in sickle cell disease. British Journal of Haematology, [s. l.], v. 205, n. 1, p. 61–70, 2024. CHOI, Y. et al. Co-occurrence of Anaerobes in Human Chronic Wounds. Microbial Ecology, [s. l.], v. 77, n. 3, p. 808–820, 2019. CHONG, K. K. L. et al. Enterococcus faecalis Modulates Immune Activation and Slows 92 Healing During Wound Infection. The Journal of Infectious Diseases, [s. l.], v. 216, n. 12, p. 1644–1654, 2017. CHONG, D. L. W. et al. Platelet-derived transforming growth factor-β1 promotes keratinocyte proliferation in cutaneous wound healing. Journal of Tissue Engineering and Regenerative Medicine, [s. l.], v. 14, n. 4, p. 645–649, 2020. CISZEK-LENDA, M. et al. Pseudomonas aeruginosa biofilm is a potent inducer of phagocyte hyperinflammation. Inflammation Research, [s. l.], v. 68, n. 5, p. 397–413, 2019. COGNASSE, F. et al. Platelets as Key Factors in Inflammation: Focus on CD40L/CD40. Frontiers in Immunology, [s. l.], v. 13, 2022. Disponível em: https://www.frontiersin.orghttps://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.825892/full. Acesso em: 24 abr. 2025. CONNES, P. et al. Vascular pathophysiology of sickle cell disease. Presse Medicale (Paris, France: 1983), [s. l.], v. 52, n. 4, p. 104202, 2023. DA SILVA, R. R. et al. Evaluation of Th17 related cytokines associated with clinical and laboratorial parameters in sickle cell anemia patients with leg ulcers. Cytokine, [s. l.], v. 65, n. 2, p. 143–147, 2014. DAVENPECK, K. L. et al. Activation of human leukocytes reduces surface P-selectin glycoprotein ligand-1 (PSGL-1, CD162) and adhesion to P-selectin in vitro. Journal of Immunology (Baltimore, Md.: 1950), [s. l.], v. 165, n. 5, p. 2764–2772, 2000. DE CATERINA, R. et al. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. The Journal of Clinical Investigation, [s. l.], v. 96, n. 1, p. 60–68, 1995. DEPREZ, K. N.; FERGUSON, J. Endobronchial Infection and Bacterial Lymphadenitis by Gemella morbillorum Leading to Airway Perforation and a Bronchopleural Fistula. Case Reports in Pulmonology, [s. l.], v. 2024, n. 1, p. 8850287, 2024. DESMOULIÈRE, A. et al. Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. The Journal of Cell Biology, [s. l.], v. 122, n. 1, p. 103–111, 1993. DEVARAJ, S.; JIALAL, I. C-Reactive Protein Polarizes Human Macrophages to an M1 Phenotype and Inhibits Transformation to the M2 Phenotype. Arteriosclerosis, Thrombosis, and Vascular Biology, [s. l.], v. 31, n. 6, p. 1397–1402, 2011. DHAMODHARAN, U. et al. Genetic association of IL-6, TNF-α and SDF-1 polymorphisms with serum cytokine levels in diabetic foot ulcer. Gene, [s. l.], v. 565, n. 1, p. 62–67, 2015. DIXIT, R. et al. Folate supplementation in people with sickle cell disease. The Cochrane Database of Systematic Reviews, [s. l.], v. 3, n. 3, p. CD011130, 2018. DOMINGOS, I. F. et al. High levels of proinflammatory cytokines IL-6 and IL-8 are associated with a poor clinical outcome in sickle cell anemia. Annals of Hematology, [s. l.], v. 99, n. 5, p. 947–953, 2020. 93 DUNYACH-REMY, C. et al. Pressure ulcers microbiota dynamics and wound evolution. Scientific Reports, [s. l.], v. 11, n. 1, p. 18506, 2021. ELALFY, M. S. et al. Immunological role of CD4+CD28null T lymphocytes, natural killer cells, and interferon-gamma in pediatric patients with sickle cell disease: relation to disease severity and response to therapy. Immunologic Research, [s. l.], v. 66, n. 4, p. 480–490, 2018. ELLIS, S.; LIN, E. J.; TARTAR, D. Immunology of Wound Healing. Current Dermatology Reports, [s. l.], v. 7, n. 4, p. 350–358, 2018a. ELLIS, S.; LIN, E. J.; TARTAR, D. Immunology of Wound Healing. Current Dermatology Reports, [s. l.], v. 7, n. 4, p. 350–358, 2018b. ESCOPY, S.; CHAIKOF, E. L. Targeting the P-selectin/PSGL-1 pathway: discovery of disease-modifying therapeutics for disorders of thromboinflammation. Blood Vessels, Thrombosis & Hemostasis, [s. l.], v. 1, n. 3, p. 100015, 2024. FASOLA, F. A. et al. The Effect of Alpha Thalassemia, HbF and HbC on Haematological Parameters of Sickle Cell Disease Patients in Ibadan, Nigeria. Mediterranean Journal of Hematology and Infectious Diseases, [s. l.], v. 14, n. 1, p. e2022001, 2022. FORTUNA, V. et al. Enhancing Sickle Cell Leg Ulcer Healing with Combined Photodynamic and Photobiomodulation Therapies: a pilot experience. Journal of Tissue Viability, [s. l.], p. 100879, 2025. FRENETTE, P. S. et al. P-Selectin Glycoprotein Ligand 1 (Psgl-1) Is Expressed on Platelets and Can Mediate Platelet–Endothelial Interactions in Vivo. The Journal of Experimental Medicine, [s. l.], v. 191, n. 8, p. 1413–1422, 2000. GHOSH, S. et al. P-selectin plays a role in haem-induced acute lung injury in sickle mice. British journal of haematology, [s. l.], v. 186, n. 2, p. 329–333, 2019. GLADWIN, M. et al. Divergent Nitric Oxide Bioavailability in Men and Women With Sickle Cell Disease. Circulation, [s. l.], v. 107, p. 271–278, 2003. GOMES, I. C. P. et al. Levels of inflammatory markers are differentially expressed in sickle cell anemia and sickle cell trait. eJHaem, [s. l.], v. 4, n. 3, p. 705–709, 2023. GRANJA, P. D. et al. Úlceras de perna em pacientes com anemia falciforme. Jornal Vascular Brasileiro, [s. l.], v. 19, p. e20200054, 2020. GRÖNWALL, C. et al. In vivo VL-targeted microbial superantigen induced global shifts in the B cell repertoire. Journal of Immunology (Baltimore, Md.: 1950), [s. l.], v. 189, n. 2, p. 850–859, 2012. GUPTA, P.; KUMAR, R. Nitric oxide: A potential etiological agent for vaso-occlusive crises in sickle cell disease. Nitric Oxide, [s. l.], v. 144, p. 40–46, 2024. HALABI-TAWIL, M. et al. Sickle cell leg ulcers: a frequently disabling complication and a marker of severity. The British Journal of Dermatology, [s. l.], v. 158, n. 2, p. 339–344, 2008. 94 HAN, Y.-P. et al. Transforming Growth Factor-β- and Tumor Necrosis Factor-α- mediated Induction and Proteolytic Activation of MMP-9 in Human Skin. The Journal of biological chemistry, [s. l.], v. 276, n. 25, p. 22341–22350, 2001. HELVACI, M. et al. Acute painful crises may be causes of sudden deaths in sickle cell diseases. [s. l.], 2023. HENRY, E. R. et al. Allosteric control of hemoglobin S fiber formation by oxygen and its relation to the pathophysiology of sickle cell disease. Proceedings of the National Academy of Sciences of the United States of America, [s. l.], v. 117, n. 26, p. 15018–15027, 2020. HEO, S. C. et al. Tumor necrosis factor-α-activated human adipose tissue-derived mesenchymal stem cells accelerate cutaneous wound healing through paracrine mechanisms. The Journal of Investigative Dermatology, [s. l.], v. 131, n. 7, p. 1559–1567, 2011. HIGDON, A. N. et al. Hemin causes mitochondrial dysfunction in endothelial cells through promoting lipid peroxidation: the protective role of autophagy. American Journal of Physiology. Heart and Circulatory Physiology, [s. l.], v. 302, n. 7, p. H1394-1409, 2012. HINES, P. C. et al. Flow adhesion of whole blood to P-selectin: a prognostic biomarker for vaso-occlusive crisis in sickle cell disease. British Journal of Haematology, [s. l.], v. 194, n. 6, p. 1074–1082, 2021a. HINES, P. C. et al. Flow adhesion of whole blood to P‐selectin: a prognostic biomarker for vaso‐occlusive crisis in sickle cell disease. British Journal of Haematology, [s. l.], v. 194, n. 6, p. 1074–1082, 2021b. HINZ, B. Formation and Function of the Myofibroblast during Tissue Repair. Journal of Investigative Dermatology, [s. l.], v. 127, n. 3, p. 526–537, 2007. HODDE, J. P.; HILES, M. C.; METZGER, D. W. Characterization of the local wound environment following treatment of chronic leg ulcers with SIS wound matrix. Journal of Tissue Viability, [s. l.], v. 29, n. 1, p. 42–47, 2020. HOSSEINI, M. et al. Skin biomechanics: a potential therapeutic intervention target to reduce scarring. Burns & Trauma, [s. l.], v. 10, p. tkac036, 2022. HOU, K. et al. Microbiota in health and diseases. Signal Transduction and Targeted Therapy, [s. l.], v. 7, n. 1, p. 1–28, 2022. HUANG, Y. et al. Rapid microbiological diagnosis based on 16S rRNA gene sequencing: A comparison of bacterial composition in diabetic foot infections and contralateral intact skin. Frontiers in Microbiology, [s. l.], v. 13, 2022. Disponível em: https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1021955/full. Acesso em: 31 mar. 2025. INGRAM, V. M. A specific chemical difference between the globins of normal human and sickle-cell anaemia haemoglobin. Nature, [s. l.], v. 178, n. 4537, p. 792–794, 1956. ISHIDA, Y. et al. CCL2-Mediated Reversal of Impaired Skin Wound Healing in Diabetic Mice by Normalization of Neovascularization and Collagen Accumulation. Journal of Investigative Dermatology, [s. l.], v. 139, n. 12, p. 2517-2527.e5, 2019. 95 ITOKUA, K. E. et al. Albuminuria, serum antioxidant enzyme levels and markers of hemolysis and inflammation in steady state children with sickle cell anemia. BMC Nephrology, [s. l.], v. 17, n. 1, p. 178, 2016. JANCIAUSKIENE, S.; VIJAYAN, V.; IMMENSCHUH, S. TLR4 Signaling by Heme and the Role of Heme-Binding Blood Proteins. Frontiers in Immunology, [s. l.], v. 11, 2020. Disponível em: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01964/full. Acesso em: 15 ago. 2024. JANG, D. et al. The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics. International Journal of Molecular Sciences, [s. l.], v. 22, n. 5, p. 2719, 2021. JANSEN, E. E. et al. Platelet-Therapeutics to Improve Tissue Regeneration and Wound Healing—Physiological Background and Methods of Preparation. Biomedicines, [s. l.], v. 9, n. 8, p. 869, 2021. JNANA, A. et al. Microbial Community Distribution and Core Microbiome in Successive Wound Grades of Individuals with Diabetic Foot Ulcers. Applied and Environmental Microbiology, [s. l.], v. 86, n. 6, p. e02608-19, 2020. JOHNSON, B. Z. et al. The Role of IL-6 in Skin Fibrosis and Cutaneous Wound Healing. Biomedicines, [s. l.], v. 8, n. 5, p. 101, 2020. JOLIBOIS, J. et al. Targeting TXNIP in endothelial progenitors mitigates IL-8-induced neutrophil recruitment under metabolic stress. Stem Cell Research & Therapy, [s. l.], v. 15, n. 1, p. 225, 2024. JURK, K.; KEHREL, B. E. Platelets: Physiology and Biochemistry. Seminars in Thrombosis and Hemostasis, [s. l.], v. 50, n. 5, p. 794–803, 2024. KALAN, L. R. et al. Strain- and Species-Level Variation in the Microbiome of Diabetic Wounds Is Associated with Clinical Outcomes and Therapeutic Efficacy. Cell Host & Microbe, [s. l.], v. 25, n. 5, p. 641-655.e5, 2019. KALIYADAN, F. et al. Prevalence and Predictive Factors for Leg Ulcers in Sickle Cell Disease Patients in Saudi Arabia: A Cross-Sectional Observational Study. Cureus, [s. l.], v. 12, n. 10, p. e11280, 2020. KANDHWAL, M. et al. Role of matrix metalloproteinase in wound healing. American Journal of Translational Research, [s. l.], v. 14, n. 7, p. 4391–4405, 2022. KARTIKA, R. W. et al. The role of VEGF, PDGF and IL-6 on diabetic foot ulcer after Platelet Rich Fibrin + hyaluronic therapy. Heliyon, [s. l.], v. 7, n. 9, 2021. Disponível em: https://www.cell.com/heliyon/abstract/S2405-8440(21)02037-5. Acesso em: 30 mar. 2025. KATO, G. J. et al. Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease. Blood, [s. l.], v. 107, n. 6, p. 2279–2285, 2006. KATO, G. J. et al. Sickle cell disease. Nature Reviews. Disease Primers, [s. l.], v. 4, p. 96 18010, 2018. KOSHY, M. et al. Leg ulcers in patients with sickle cell disease [see comments]. Blood, [s. l.], v. 74, n. 4, p. 1403–1408, 1989. KOTTNER, J. et al. Pressure ulcer/injury classification today: An international perspective. Journal of Tissue Viability, [s. l.], v. 29, n. 3, p. 197–203, 2020. KUNIMITSU, M. et al. Relationship between healing status and microbial dissimilarity in wound and peri-wound skin in pressure injuries. Journal of Tissue Viability, [s. l.], v. 32, n. 1, p. 144–150, 2023. L. BOWLING, F.; U. DISSANAYAKE, S.; B. JUDE, E. Opportunistic Pathogens in Diabetic Foot Lesions. Current Diabetes Reviews, [s. l.], v. 8, n. 3, p. 195–199, 2012. LADIZINSKI, B. et al. Sickle Cell Disease and Leg Ulcers. Advances in Skin & Wound Care, [s. l.], v. 25, n. 9, p. 420, 2012a. LADIZINSKI, B. et al. Sickle cell disease and leg ulcers. Advances in Skin & Wound Care, [s. l.], v. 25, n. 9, p. 420–428, 2012b. LAI, Y. et al. Commensal bacteria regulate TLR3-dependent inflammation following skin injury. Nature medicine, [s. l.], v. 15, n. 12, p. 1377–1382, 2009. LANARO, C. et al. Altered levels of cytokines and inflammatory mediators in plasma and leukocytes of sickle cell anemia patients and effects of hydroxyurea therapy. Journal of Leukocyte Biology, [s. l.], v. 85, n. 2, p. 235–242, 2009. LANDÉN, N. X.; LI, D.; STÅHLE, M. Transition from inflammation to proliferation: a critical step during wound healing. Cellular and Molecular Life Sciences, [s. l.], v. 73, n. 20, p. 3861–3885, 2016. LEID, J. G. et al. The Exopolysaccharide Alginate Protects Pseudomonas aeruginosa Biofilm Bacteria from IFN-γ-Mediated Macrophage Killing1. The Journal of Immunology, [s. l.], v. 175, n. 11, p. 7512–7518, 2005. LI, Y. et al. Sequence analysis of microbiota in clinical human cases with diabetic foot ulcers from China. Heliyon, [s. l.], v. 10, n. 14, 2024. Disponível em: https://www.cell.com/heliyon/abstract/S2405-8440(24)10399-4. Acesso em: 26 mar. 2025. LI, D. et al. Single-Cell Analysis Reveals Major Histocompatibility Complex II‒Expressing Keratinocytes in Pressure Ulcers with Worse Healing Outcomes. Journal of Investigative Dermatology, [s. l.], v. 142, n. 3, p. 705–716, 2022. LIGI, D. et al. Chronic venous disease – Part I: Inflammatory biomarkers in wound healing. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, [s. l.], v. 1862, n. 10, p. 1964–1974, 2016. LIMA, K. T. L. L. et al. Qualidade de vida dos portadores de doença falciforme. Rev. enferm. UFPE on line, [s. l.], p. 424–430, 2019. LIN, M.-H. et al. Enhancing wound healing in recalcitrant leg ulcers with aminolevulinic 97 acid-mediated antimicrobial photodynamic therapy. Photodiagnosis and Photodynamic Therapy, [s. l.], v. 33, p. 102149, 2021. LIN, S. et al. Heme activates TLR4-mediated inflammatory injury via MyD88/TRIF signaling pathway in intracerebral hemorrhage. Journal of Neuroinflammation, [s. l.], v. 9, n. 1, p. 46, 2012. LITTIG, J. P. B. et al. Increased Population of CD40+ Fibroblasts Is Associated with Impaired Wound Healing and Chronic Inflammation in Diabetic Foot Ulcers. Journal of Clinical Medicine, [s. l.], v. 11, n. 21, p. 6335, 2022. LIU, X. et al. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell, [s. l.], v. 86, n. 1, p. 147–157, 1996. LOBO, C. L. de C. et al. Mortality in children, adolescents and adults with sickle cell anemia in Rio de Janeiro, Brazil. Revista Brasileira De Hematologia E Hemoterapia, [s. l.], v. 40, n. 1, p. 37–42, 2018. LOOMIS, K. H. et al. A mixed community of skin microbiome representatives influences cutaneous processes more than individual members. Microbiome, [s. l.], v. 9, n. 1, p. 22, 2021. MAHESWARY, T.; NURUL, A. A.; FAUZI, M. B. The Insights of Microbes’ Roles in Wound Healing: A Comprehensive Review. Pharmaceutics, [s. l.], v. 13, n. 7, p. 981, 2021. MAHMOUD, N. N. et al. Investigating Inflammatory Markers in Wound Healing: Understanding Implications and Identifying Artifacts. ACS Pharmacology & Translational Science, [s. l.], v. 7, n. 1, p. 18–27, 2024a. MAHMOUD, N. N. et al. Investigating Inflammatory Markers in Wound Healing: Understanding Implications and Identifying Artifacts. ACS Pharmacology & Translational Science, [s. l.], v. 7, n. 1, p. 18–27, 2024b. MANZO MARGIOTTA, F. et al. Monoclonal Antibodies in the Management of Inflammation in Wound Healing: An Updated Literature Review. Journal of Clinical Medicine, [s. l.], v. 13, n. 14, p. 4089, 2024. MAROTTA, C. A. et al. Human beta-globin messenger RNA. III. Nucleotide sequences derived from complementary DNA. The Journal of Biological Chemistry, [s. l.], v. 252, n. 14, p. 5040–5053, 1977. MATHEUS, G. G. et al. Understanding the pathophysiology of Pseudomonas aeruginosa colonization as a guide for future treatment for chronic leg ulcers. Burns & Trauma, [s. l.], v. 13, p. tkae083, 2025. MCCARTY, S. M.; PERCIVAL, S. L. Proteases and Delayed Wound Healing. Advances in Wound Care, [s. l.], v. 2, n. 8, p. 438–447, 2013. MCDONALD, B. et al. Intravascular Danger Signals Guide Neutrophils to Sites of Sterile Inflammation. Science, [s. l.], v. 330, n. 6002, p. 362–366, 2010. MCMAHON, T. J. et al. Nitric oxide loading reduces sickle red cell adhesion and 98 vaso-occlusion in vivo. Blood Advances, [s. l.], v. 3, n. 17, p. 2586–2597, 2019. MENDONÇA, R.; SILVEIRA, A. A. A.; CONRAN, N. Red cell DAMPs and inflammation. Inflammation Research, [s. l.], v. 65, n. 9, p. 665–678, 2016. MIKOSIŃSKI, J. et al. Longitudinal Evaluation of Biomarkers in Wound Fluids from Venous Leg Ulcers and Split-thickness Skin Graft Donor Site Wounds Treated with a Protease-modulating Wound Dressing. Acta Dermato-Venereologica, [s. l.], v. 102, p. adv00834, 2022. MINNITI, C. P. et al. The impact of voxelotor treatment on leg ulcers in patients with sickle cell disease. American Journal of Hematology, [s. l.], v. 96, n. 4, p. E126–E128, 2021a. MINNITI, C. P. et al. The impact of voxelotor treatment on leg ulcers in patients with sickle cell disease. American Journal of Hematology, [s. l.], v. 96, n. 4, p. E126–E128, 2021b. MINNITI, C. P. et al. Vasculopathy, inflammation, and blood flow in leg ulcers of patients with sickle cell anemia. American journal of hematology, [s. l.], v. 89, n. 1, p. 1–6, 2014. MINNITI, C. P.; KATO, G. J. Critical Reviews: How we treat sickle cell patients with leg ulcers. American Journal of Hematology, [s. l.], v. 91, n. 1, p. 22–30, 2016. MOFFATT, C. J. et al. Prevalence of leg ulceration in a London population. QJM: An International Journal of Medicine, [s. l.], v. 97, n. 7, p. 431–437, 2004. MONDORO, T. H. et al. Biological action of nitric oxide donor compounds on platelets from patients with sickle cell disease. British Journal of Haematology, [s. l.], v. 112, n. 4, p. 1048–1054, 2001. MONFORT, J.-B.; SENET, P. Leg Ulcers in Sickle-Cell Disease: Treatment Update. Advances in Wound Care, [s. l.], v. 9, n. 6, p. 348–356, 2020. MORIKIS, V. A. et al. Targeting Neutrophil Adhesive Events to Address Vaso-Occlusive Crisis in Sickle Cell Patients. Frontiers in Immunology, [s. l.], v. 12, 2021. Disponível em: https://www.frontiersin.orghttps://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.663886/full. Acesso em: 27 abr. 2025. MUÑOZ-CALLEJAS, A. et al. Low P-Selectin Glycoprotein Ligand-1 Expression in Neutrophils Associates with Disease Activity and Deregulated NET Formation in Systemic Lupus Erythematosus. International Journal of Molecular Sciences, [s. l.], v. 24, n. 7, p. 6144, 2023. MURPHY, E. C. et al. Identification of molecular mechanisms used by inegoldia magna to penetrate and colonize human skin. Molecular Microbiology, [s. l.], v. 94, n. 2, p. 403–417, 2014. NADER, E.; ROMANA, M.; CONNES, P. The Red Blood Cell-Inflammation Vicious Circle in Sickle Cell Disease. Frontiers in Immunology, [s. l.], v. 11, p. 454, 2020. NG, C. T. et al. Interferon-Gamma Increases Endothelial Permeability by Causing Activation of p38 MAP Kinase and Actin Cytoskeleton Alteration. Journal of Interferon & Cytokine Research: The Official Journal of the International Society for Interferon and Cytokine 99 Research, [s. l.], v. 35, n. 7, p. 513–522, 2015. OBEAGU, E. I. et al. An Update on Interferon Gamma and C Reactive Proteins in Sickle Cell Anaemia Crisis. [s. l.], 2022. Disponível em: http://hdl.handle.net/20.500.12493/14519. Acesso em: 27 abr. 2025. OKPALA, I. et al. Relationship between the clinical manifestations of sickle cell disease and the expression of adhesion molecules on white blood cells. European Journal of Haematology, [s. l.], v. 69, n. 3, p. 135–144, 2002. OLATUNYA, O. S. et al. Evaluation of sociodemographic, clinical, and laboratory markers of sickle leg ulcers among young nigerians at a tertiary health institution. Nigerian Journal of Clinical Practice, [s. l.], v. 21, n. 7, p. 882–887, 2018. OLIVEIRA, F. M. de. Caracterização do microbioma em úlcera de perna de pacientes com Doença Falciforme. 2023a. text - Universidade de São Paulo, [s. l.], 2023. Disponível em: https://www.teses.usp.br/teses/disponiveis/5/5134/tde-29052023-163729/. Acesso em: 23 set. 2024. OLIVEIRA, F. M. de. Caracterização do microbioma em úlcera de perna de pacientes com Doença Falciforme. [S. l.], 2023b. PAULING, L. et al. Sickle Cell Anemia, a Molecular Disease. Science, [s. l.], v. 110, n. 2865, p. 543–548, 1949. PIIPPONEN, M.; LI, D.; LANDÉN, N. X. The Immune Functions of Keratinocytes in Skin Wound Healing. International Journal of Molecular Sciences, [s. l.], v. 21, n. 22, p. 8790, 2020a. PIIPPONEN, M.; LI, D.; LANDÉN, N. X. The Immune Functions of Keratinocytes in Skin Wound Healing. International Journal of Molecular Sciences, [s. l.], v. 21, n. 22, p. 8790, 2020b. PUKSTAD, B. S. et al. Non-healing is associated with persistent stimulation of the innate immune response in chronic venous leg ulcers. Journal of Dermatological Science, [s. l.], v. 59, n. 2, p. 115–122, 2010. QIAN, L.-W. et al. Exacerbated and prolonged inflammation impairs wound healing and increases scarring. Wound Repair and Regeneration, [s. l.], v. 24, n. 1, p. 26–34, 2016. RAFFETTO, J. D. et al. Why Venous Leg Ulcers Have Difficulty Healing: Overview on Pathophysiology, Clinical Consequences, and Treatment. Journal of Clinical Medicine, [s. l.], v. 10, n. 1, p. 29, 2021. RAZIYEVA, K. et al. Immunology of Acute and Chronic Wound Healing. Biomolecules, [s. l.], v. 11, n. 5, p. 700, 2021. RIDIANDRIES, A.; TAN, J. T. M.; BURSILL, C. A. The Role of Chemokines in Wound Healing. International Journal of Molecular Sciences, [s. l.], v. 19, n. 10, p. 3217, 2018. RIFKIND, J. M.; MOHANTY, J. G.; NAGABABU, E. The pathophysiology of extracellular hemoglobin associated with enhanced oxidative reactions. Frontiers in Physiology, [s. l.], v. 100 5, p. 500, 2014. SALOMONE, F. et al. Unconjugated bilirubin, a potent endogenous antioxidant, is decreased in patients with non-alcoholic steatohepatitis and advanced fibrosis. Journal of Gastroenterology and Hepatology, [s. l.], v. 28, n. 7, p. 1202–1208, 2013. SANTOS, E. do C. et al. Leg Ulcers in Sickle Cell Disease: A Multifactorial Analysis Highlights the Hemolytic Profile. Hematology Reports, [s. l.], v. 15, n. 1, p. 119–129, 2023. SCHECHTER, A. N. Sickle cell anaemia therapy in 2025. British Journal of Haematology, [s. l.], v. 206, n. 3, p. 842–845, 2025. SCHULTZ, G. S. et al. Principles of Wound Healing. In: FITRIDGE, R.; THOMPSON, M. (org.). Mechanisms of Vascular Disease: A Reference Book for Vascular Specialists. Adelaide (AU): University of Adelaide Press, 2011. Disponível em: http://www.ncbi.nlm.nih.gov/books/NBK534261/. Acesso em: 16 ago. 2024. SERJEANT, G. R. Leg Ulceration in Sickle Cell Anemia. Archives of Internal Medicine, [s. l.], v. 133, n. 4, p. 690–694, 1974. SERJEANT, G. R. et al. Leg ulceration in sickle cell disease: medieval medicine in a modern world. Hematology/Oncology Clinics of North America, [s. l.], v. 19, n. 5, p. 943–956, viii–ix, 2005. SERRA, R. et al. Extracellular matrix assessment of infected chronic venous leg ulcers: role of metalloproteinases and inflammatory cytokines. International Wound Journal, [s. l.], v. 13, n. 1, p. 53–58, 2014. SHARMA, C. et al. The role of matrix metalloproteinase-9 and its inhibitor TIMP-1 in burn injury: a systematic review. International Journal of Burns and Trauma, [s. l.], v. 11, n. 4, p. 275–288, 2021. SHETTY, P.; DSOUZA, R.; KUMAR B, V. Matrix Metalloproteinase-9 as a Predictor of Healing in Diabetic Foot Ulcers. Cureus, [s. l.], 2024. Disponível em: https://www.cureus.com/articles/323401-matrix-metalloproteinase-9-as-a-predictor-of-healing-in-diabetic-foot-ulcers. Acesso em: 30 mar. 2025. SIMKA, M. Delayed healing of chronic leg ulcers can result from impaired trafficking of bone marrow-derived precursors of keratinocytes to the skin. Medical Hypotheses, [s. l.], v. 69, n. 3, p. 637–641, 2007. SINGH, A. P.; MINNITI, C. P. Leg Ulceration in Sickle Cell Disease: An Early and Visible Sign of End‐Organ Disease. In: LEG ULCERATION IN SICKLE CELL DISEASE, 2016. (B. P. D. Inusa, Org.)Anais [...]. [S. l.]: InTech, 2016. Disponível em: http://www.intechopen.com/books/sickle-cell-disease-pain-and-common-chronic-complications/leg-ulceration-in-sickle-cell-disease-an-early-and-visible-sign-of-end-organ-disease. Acesso em: 31 mar. 2025. SMITH, B. et al. Chronic Edema Management of the Lower Extremities. Cureus, [s. l.], 2024. Disponível em: https://www.cureus.com/articles/261171-chronic-edema-management-of-the-lower-extremities. Acesso em: 9 maio 2025. 101 SMITH, K. et al. One step closer to understanding the role of bacteria in diabetic foot ulcers: characterising the microbiome of ulcers. BMC Microbiology, [s. l.], v. 16, n. 1, p. 54, 2016. SOUZA, V. R. de et al. Factors Associated with Leg Ulcers in Adults with Sickle Cell Disease in Brazil. [s. l.], 2023. Disponível em: https://observatorio.fm.usp.br/handle/OPI/53116. Acesso em: 16 ago. 2024. SPIRA, J. A. O. et al. Doença falciforme: cuidado com pessoas com úlcera da perna nos serviços de atenção à saúde. Revista Enfermagem UERJ, [s. l.], v. 32, p. e79186–e79186, 2024. SPIRA, J. A. O. et al. Estimated costs in treating sickle cell disease leg ulcer. Revista da Escola de Enfermagem da USP, [s. l.], v. 54, p. e03582, 2020. SPIRA, J. A. O. et al. Prevalence of people with sickle cell disease and leg ulcers in Brazil: Socioeconomic and clinical overview. PloS One, [s. l.], v. 17, n. 9, p. e0274254, 2022. STODDARD, K.; SOHAL, M.; BEDSON, R. Anaesthetic management of patients with sickle cell disease in obstetrics. BJA Education, [s. l.], v. 22, n. 3, p. 87–93, 2022. STOJADINOVIC, O. et al. Deregulation of keratinocyte differentiation and activation: a hallmark of venous ulcers. Journal of Cellular and Molecular Medicine, [s. l.], v. 12, n. 6b, p. 2675–2690, 2008. TAN, J. et al. Tissue and urinary haemosiderin in chronic leg ulcers. European Journal of Vascular and Endovascular Surgery: The Official Journal of the European Society for Vascular Surgery, [s. l.], v. 34, n. 3, p. 355–360, 2007. TANAKA, T.; NARAZAKI, M.; KISHIMOTO, T. IL-6 in Inflammation, Immunity, and Disease. Cold Spring Harbor Perspectives in Biology, [s. l.], v. 6, n. 10, p. a016295, 2014. TELES, W. et al. Frequência de casos de anemia falciforme, transfusão e tratamento – Experiência de um centro de hemoterapia em uma região do nordeste brasileiro / Frequency of sickle cell anemia cases, transfusion and treatment - Experience of a hemotherapy center in a region of northeastern Brazil. Brazilian Journal of Health Review, [s. l.], v. 4, p. 20426–20441, 2021. THOMSON, A. M. et al. Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000–2021: a systematic analysis from the Global Burden of Disease Study 2021. The Lancet Haematology, [s. l.], v. 10, n. 8, p. e585–e599, 2023. TOYGAR, I.; SIMSIR, I. Y.; CETINKALP, S. Evaluation of three different techniques for measuring wound area in diabetic foot ulcers: a reproducibility study. Journal of Wound Care, [s. l.], v. 29, n. 9, p. 518–524, 2020. TSIOUMPEKOU, M. et al. The Role of Cytokines in Neutrophil Development, Tissue Homing, Function and Plasticity in Health and Disease. Cells, [s. l.], v. 12, n. 15, p. 1981, 2023. UBEROI, A.; MCCREADY-VANGI, A.; GRICE, E. A. The wound microbiota: microbial mechanisms of impaired wound healing and infection. Nature Reviews Microbiology, [s. l.], v. 22, n. 8, p. 507–521, 2024a. 102 UBEROI, A.; MCCREADY-VANGI, A.; GRICE, E. A. The wound microbiota: microbial mechanisms of impaired wound healing and infection. Nature Reviews Microbiology, [s. l.], v. 22, n. 8, p. 507–521, 2024b. VALENZUELA, N. M. IFNγ, and to a Lesser Extent TNFα, Provokes a Sustained Endothelial Costimulatory Phenotype. Frontiers in Immunology, [s. l.], v. 12, p. 648946, 2021. VAN LOO, G.; BERTRAND, M. J. M. Death by TNF: a road to inflammation. Nature Reviews Immunology, [s. l.], v. 23, n. 5, p. 289–303, 2023. VELUSAMY, P. et al. IL-6 Contributes to Impaired Nitric Oxide and Increased Mitochondrial ROS Production in Human Aortic Endothelial Cells. Physiology, [s. l.], v. 39, n. S1, p. 2062, 2024. VICARI, P. et al. Interleukin-1β and interleukin-6 gene polymorphisms are associated with manifestations of sickle cell anemia. Blood Cells, Molecules & Diseases, [s. l.], v. 54, n. 3, p. 244–249, 2015. VOUILLARMET, J. et al. Advanced glycation end products assessed by skin autofluorescence: a new marker of diabetic foot ulceration. Diabetes Technology & Therapeutics, [s. l.], v. 15, n. 7, p. 601–605, 2013. WADUD, R. et al. Yoda1 and phosphatidylserine exposure in red cells from patients with sickle cell anaemia. Scientific Reports, [s. l.], v. 10, n. 1, p. 20110, 2020. WANG, Y. et al. [Protein expressions of matrix metalloproteinase-9 and its inhibitor and their ratio changes in wound healing of patients with stages Ⅲ and Ⅳ pressure ulcers]. Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns, [s. l.], v. 35, n. 10, p. 746–751, 2019. WEINZWEIG, N. et al. Lower Limb Salvage by Microvascular Free-Tissue Transfer in Patients with Homozygous Sickle Cell Disease. Plastic and Reconstructive Surgery, [s. l.], v. 96, n. 5, p. 1154, 1995. WILLENBORG, S.; INJARABIAN, L.; EMING, S. A. Role of Macrophages in Wound Healing. Cold Spring Harbor Perspectives in Biology, [s. l.], v. 14, n. 12, p. a041216, 2022. WOOD, S. et al. Pro-Inflammatory Chemokine CCL2 (MCP-1) Promotes Healing in Diabetic Wounds by Restoring the Macrophage Response. PLOS ONE, [s. l.], v. 9, n. 3, p. e91574, 2014. XU, Q. et al. Neutrophil reverse migration. Journal of Inflammation (London, England), [s. l.], v. 19, p. 22, 2022. YAHOUÉDÉHOU, S. C. M. A. et al. Sickle Cell Anemia: Variants in the CYP2D6, CAT, and SLC14A1 Genes Are Associated With Improved Hydroxyurea Response. Frontiers in Pharmacology, [s. l.], v. 11, 2020. Disponível em: https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.553064/full. Acesso em: 15 ago. 2024. YOUNESI, F. S. et al. Fibroblast and myofibroblast activation in normal tissue repair and fibrosis. Nature Reviews Molecular Cell Biology, [s. l.], v. 25, n. 8, p. 617–638, 2024. 103 YOUSIF, T. Y. E. Impact of Abnormal Leukocyte Count in the Pathophysiology of Sickle Cell Anemia. Journal of Blood Medicine, [s. l.], v. 13, p. 673–679, 2022. ZHANG, L.; LEVY, A.; RIFKIND, J. M. Autoxidation of hemoglobin enhanced by dissociation into dimers. The Journal of Biological Chemistry, [s. l.], v. 266, n. 36, p. 24698–24701, 1991. ZHENG, D. et al. ROS-triggered endothelial cell death mechanisms: Focus on pyroptosis, parthanatos, and ferroptosis. Frontiers in Immunology, [s. l.], v. 13, p. 1039241, 2022. ZHU, Y. et al. Preventive effect of cluster nursing on pressure ulcers in orthopedic patients and predictive value of serum IL-6 and TNF-α for the occurrence of pressure ulcers. American Journal of Translational Research, [s. l.], v. 15, n. 2, p. 1140–1149, 2023. ŽIBERNA, L.; JENKO-PRAŽNIKAR, Z.; PETELIN, A. Serum Bilirubin Levels in Overweight and Obese Individuals: The Importance of Anti-Inflammatory and Antioxidant Responses. Antioxidants, [s. l.], v. 10, n. 9, p. 1352, 2021. ZILLMER, R. et al. Duration of wound fluid secretion from chronic venous leg ulcers is critical for interleukin-1α, interleukin-1β, interleukin-8 levels and fibroblast activation. Archives of Dermatological Research, [s. l.], v. 303, n. 8, p. 601–606, 2011a. ZILLMER, R. et al. Duration of wound fluid secretion from chronic venous leg ulcers is critical for interleukin-1α, interleukin-1β, interleukin-8 levels and fibroblast activation. Archives of Dermatological Research, [s. l.], v. 303, n. 8, p. 601–606, 2011b. | pt_BR |
| dc.type.degree | Mestrado Acadêmico | pt_BR |