ABSTRACT
To explore the effectiveness and safety of a Chinese medicinal decoction Wuwei Xiaodu Drink (WWXDD) in inhibiting chronic osteomyelitis via regulatory T cells signaling. The effective constitutes of WWXDD and osteomyelitis related genes were screened. Target proteins were cross-validated using the Venny database. GO function and KEGG pathway analysis were performed for target proteins, while pharmacological network was constructed. The bone properties were analyzed by HE staining and the concentrations of immune factors were measured by ELISA. The expression of CTLA-4 and Foxp3 mRNA and STAT5, p-STAT5, CTLA-4 and Foxp3 protein were detected using Real-time PCR and Western blot, respectively. FACS was used to analyze the percentages of cells. A total of 117 genes overlapped between 785 target genes of the active compounds of WWXDD and 912 osteomyelitis related genes. Inflammation-related genes, including IL-6, TNFα, IL-1β and IL-2 showed high connection degree in the drug-compound-disease-target network. GO function and KEGG pathway analysis revealed that 117 intersection genes mainly enriched in virus infection related pathways, immune related pathways and chemokine signaling pathway. Furthermore, the development of chronic osteomyelitis was suppressed in model rats after treatment with WWXDD. Meanwhile, the concentrations of IL-2 and CD4+CD25+Foxp3 Treg percentages together with the levels of p-STAT5, CTLA-4 and Foxp3 were also down-regulated. Furthermore, IL-2 and WWXDD drug-containing serum exhibited opposite effects on regulating IL-2, IL-10, TGF-β1, Foxp3, CTLA4 and STAT5. In addition, a STAT5 phosphorylation inhibitor suppressed the expression of Foxp3 and CTLA-4. WWXDD can treat chronic osteomyelitis through suppressing the main regulating factors of Tregs and interfere its immunodepression. Our results bring a new solution for chronic osteomyelitis.
Subject(s)
Animals , Rats , Forkhead Transcription Factors/metabolism , Interleukin-2/metabolism , Osteomyelitis/metabolism , STAT5 Transcription Factor/metabolism , Signal Transduction , T-Lymphocytes, RegulatoryABSTRACT
La enfermedad granulomatosa crónica es una inmunodeficiencia primaria infrecuente, debida a un defecto en la actividad microbicida de los fagocitos, originada por mutaciones en los genes que codifican alguna de las subunidades del complejo enzimático nicotinamida adenina dinucleótido fosfato oxidasa. La incidencia estimada es 1 en 250 000 recién nacidos vivos. Puede presentarse desde la infancia hasta la adultez, por lo general, en menores de 2 años. Las infecciones bacterianas y fúngicas, en conjunto con las lesiones granulomatosas, son las manifestaciones más habituales de la enfermedad. Los microorganismos aislados más frecuentemente son Aspergillus spp., Staphylococcus aureus, Serratia marcescens, Nocardia spp. Se reporta el caso clínico de un varón de 1 año de vida en el que se diagnosticó enfermedad granulomatosa crónica a partir de infecciones múltiples que ocurrieron simultáneamente: aspergilosis pulmonar invasiva, osteomielitis por Serratia marcescens y granuloma cervical por Enterobacter cloacae.
Chronic granulomatous disease is an uncommon primary immunodeficiency due to a defect of the killing activity of phagocytes, caused by mutations in any of the genes encoding subunits of the superoxide-generating phagocyte NADPH oxidase system. The incidence is 1 in 250 000 live births. It can occur from infancy to adulthood, usually in children under 2 years. Bacterial and fungal infections in association with granuloma lesions are the most common manifestations of the disease. Aspergillus species, Staphylococcus aureus, Serratia marcescens, Nocardia species are the most common microorganisms isolated. We describe here a case of a 1-year-old boy with chronic granulomatous disease and invasive pulmonary aspergillosis, Serratia marcescens osteomyelitis and Enterobacter cloacae cervical granuloma.
Subject(s)
Humans , Male , Infant , Serratia Infections/diagnosis , Enterobacteriaceae Infections/diagnosis , Pulmonary Aspergillosis/diagnosis , Granulomatous Disease, Chronic/diagnosis , Osteomyelitis/diagnosis , Osteomyelitis/metabolism , Serratia marcescens/isolation & purification , Serratia Infections/microbiology , Enterobacter cloacae/isolation & purification , Enterobacteriaceae Infections/microbiology , Granulomatous Disease, Chronic/microbiologyABSTRACT
OBJETIVO: O diagnóstico de osteomielite crônica em atividade ou sobreposta a outras patologias é difícil, pois estas situações mascaram os achados radiológicos de infecção. A especificidade da cintilografia do esqueleto ou com gálio-67 também é reduzida pela influência da remodelação óssea na captação destes radiofármacos. Anticorpos policlonais marcados com tecnécio-99m (Tc-99m-IgG) apresentam captação independente do metabolismo ósseo, sendo um dos radiofármacos em investigação para avaliação mais específica de infecção. CASUÍSTICA E MÉTODO: Neste estudo comparou-se a cintilografia com Tc-99m-IgG, cintilografia óssea trifásica e cintilografia com gálio-67 no diagnóstico da osteomielite crônica em atividade em 23 segmentos ósseos; correlacionando-as com dados clínico-laboratoriais e radiológicos. RESULTADOS: Oito dos 23 segmentos foram classificados como infectados, 11 não infectados e quatro inconclusivos. A sensibilidade e especificidade encontradas para cintilografia óssea, com gálio-67 e com Tc-99m-IgG foram, respectivamente, 88 e 36 por cento, 75 e 73 por cento, 88 e 82 por cento. CONCLUSÃO: Os resultados sugerem que a Tc-99m-IgG possa ser utilizada no diagnóstico da osteomielite crônica em atividade.