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1.
Article in English | WPRIM | ID: wpr-929250

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 , Forkhead Transcription Factors/metabolism , Interleukin-2/metabolism , Osteomyelitis/metabolism , Rats , STAT5 Transcription Factor/metabolism , Signal Transduction , T-Lymphocytes, Regulatory
2.
Biol. Res ; 52: 59, 2019. graf
Article in English | LILACS | ID: biblio-1100911

ABSTRACT

OBJECTIVES: In varicose veins, vascular smooth muscle cells (VSMCs) often shows phenotypic transition and abnormal proliferation and migration. Evidence suggests the FOXC2-Notch pathway may be involved in the pathogenesis of varicose veins. Here, this study aimed to explore the role of long non-coding RNA FOXC2-AS1 (FOXC2 antisense RNA 1) in phenotypic transition, proliferation, and migration of varicose vein-derived VSMCs and to explore whether the FOXC2-Notch pathway was involved in this process. METHODS: The effect of FOXC2-AS1 on the proliferation and migration of human great saphenous vein smooth muscle cells (SV-SMCs) was analyzed using MTT assay and Transwell migration assay, respectively. The levels of contractile marker SM22α and synthetic marker osteopontin were measured by immunohistochemistry and Western blot to assess the phenotypic transition. RESULTS: The human varicose veins showed thickened intima, media and adventitia layers, increased synthetic VSMCs, as well as upregulated FOXC2-AS1 and FOXC2 expression. In vitro assays showed that FOXC2-AS1 overexpression promoted phenotypic transition, proliferation, and migration of SV-SMCs. However, the effect of FOXC2-AS1 overexpression could be abrogated by both FOXC2 silencing and the Notch signaling inhibitor FLI-06. Furthermore, FOXC2-AS1 overexpression activated the Notch pathway by upregulating FOXC2. CONCLUSION: FOXC2-AS1 overexpression promotes phenotypic transition, proliferation, and migration of SV-SMCs, at least partially, by activating the FOXC2-Notch pathway.


Subject(s)
Humans , Saphenous Vein/metabolism , Cell Movement/physiology , Myocytes, Smooth Muscle/metabolism , Cell Proliferation/physiology , Forkhead Transcription Factors/metabolism , Phenotype , Saphenous Vein/pathology , Signal Transduction , Up-Regulation , Cells, Cultured , Myocytes, Smooth Muscle/pathology
3.
Rev. latinoam. enferm ; 23(2): 234-241, Feb-Apr/2015. tab, graf
Article in English | LILACS, BDENF | ID: lil-747177

ABSTRACT

OBJECTIVE: to analyze the efficacy of the Nursing Process in an Intensive Care Unit using indicators generated by software. METHOD: cross-sectional study using data collected for four months. RNs and students daily registered patients, took history (at admission), performed physical assessments, and established nursing diagnoses, nursing plans/prescriptions, and assessed care delivered to 17 patients using software. Indicators concerning the incidence and prevalence of nursing diagnoses, rate of effectiveness, risk diagnoses, and rate of effective prevention of complications were computed. RESULTS: the Risk for imbalanced body temperature was the most frequent diagnosis (23.53%), while the least frequent was Risk for constipation (0%). The Risk for Impaired skin integrity was prevalent in 100% of the patients, while Risk for acute confusion was the least prevalent (11.76%). Risk for constipation and Risk for impaired skin integrity obtained a rate of risk diagnostic effectiveness of 100%. The rate of effective prevention of acute confusion and falls was 100%. CONCLUSION: the efficacy of the Nursing Process using indicators was analyzed because these indicators reveal how nurses have identified patients' risks and conditions, and planned care in a systematized manner. .


OBJETIVO: analisar a eficácia do Processo de Enfermagem em uma Unidade de Terapia Intensiva, utilizando indicadores gerados por um software. MÉTODO: estudo transversal, cujos dados foram coletados durante quatro meses. Enfermeiros e acadêmicos realizaram, diariamente, cadastro e anamnese (na admissão), exame físico, diagnósticos de enfermagem, planejamento/prescrição de enfermagem e avaliação da assistência de 17 pacientes, utilizando um software. Calculou-se os indicadores incidência e prevalência de diagnósticos de enfermagem, taxa de efetividade diagnóstica de risco e taxa de efetividade na prevenção de complicações. RESULTADOS: o Risco de desequilíbrio na temperatura corporal foi o diagnóstico mais incidente (23,53%) e o menos incidente foi o Risco de constipação (0%). O Risco de integridade da pele prejudicada foi prevalente em 100% dos pacientes, enquanto o Risco de confusão aguda foi o menos prevalente (11,76%). Risco de constipação e Risco de integridade da pele prejudicada obtiveram taxa de efetividade diagnóstica de risco de 100%. A taxa de efetividade na prevenção de confusão aguda e de queda foi de 100%. CONCLUSÃO: analisou-se a eficácia do Processo de Enfermagem utilizando indicadores, pois retratam como o enfermeiro tem identificado os problemas e riscos do paciente, e planejado a assistência de forma sistematizada. .


OBJETIVO: analizar la eficacia del Proceso de Enfermería en una Unidad de Terapia Intensiva, utilizando indicadores generados por un software. MÉTODO: estudio transversal, cuyos datos fueron recolectados durante cuatro meses. Enfermeros y académicos realizaron, diariamente, registro y anamnesis (en la admisión), examen físico, diagnósticos de enfermería, planificación/prescripción de enfermería y evaluación de la asistencia en 17 pacientes, utilizando un software. Se calculó los indicadores incidencia y prevalencia de diagnósticos de enfermería, la tasa de efectividad diagnóstica de riesgo y la tasa de efectividad en la prevención de complicaciones. RESULTADOS: el Riesgo de desequilibrio en la temperatura corporal fue el diagnóstico más prevalente (23,53%) y el menos prevalente fue el Riesgo de constipación (0%). El Riesgo de integridad de la piel perjudicada fue prevalente en 100% de los pacientes, en cuanto el Riesgo de confusión aguda fue el menos prevalente (11,76%). El Riesgo de constipación y el Riesgo de integridad de la piel perjudicada obtuvieron una tasa de efectividad diagnóstica de riesgo de 100%. La tasa de efectividad en la prevención de confusión aguda y de caída fue de 100%. CONCLUSIÓN: se analizó la eficacia del Proceso de Enfermería utilizando indicadores, ya que retratan cómo el enfermero ha identificado los problemas y riesgos del paciente, y planificado la asistencia de forma sistematizada. .


Subject(s)
Animals , Male , Mice , Islets of Langerhans Transplantation , Forkhead Transcription Factors/metabolism , Freund's Adjuvant/immunology , Freund's Adjuvant/pharmacology , Graft Rejection/immunology , Immunotherapy , Interferon-gamma/metabolism , /metabolism , Islets of Langerhans/cytology , Islets of Langerhans/metabolism , Lipids/immunology , Lipids/pharmacology , Mice, Inbred BALB C , Spleen/drug effects , Spleen/radiation effects , Transplantation, Homologous , Th1 Cells/immunology , Th1 Cells/metabolism , Tumor Necrosis Factor-alpha/metabolism
4.
Dental press j. orthod. (Impr.) ; 20(1): 45-51, Jan-Feb/2015. tab, graf
Article in English | LILACS | ID: lil-741446

ABSTRACT

INTRODUCTION: The consensus about the relationship between TMD and orthodontic treatment has gone from a cause and effect association between TMD and orthodontic treatment to the idea that there is no reliable evidence supporting this statement. OBJECTIVE: To assess the beliefs, despite scientific evidence, of Brazilian orthodontists about the relationship between TMD and orthodontic treatment with regards to treatment, prevention and etiology of TMD. METHODS: A survey about the relationship between TMD and orthodontic treatment was prepared and sent to Brazilian orthodontists by e-mail and social networks. Answers were treated by means of descriptive statistics and strong associations between variables were assessed by qui-square test. RESULTS: The majority of orthodontists believe that orthodontic treatment not only is not the best treatment option for TMD, but also is not able to prevent TMD. Nevertheless, the majority of orthodontists believe that orthodontic treatment can cause TMD symptoms. CONCLUSION: This study suggests that orthodontists' beliefs about the relationship between orthodontic treatment and TMD are in accordance with scientific evidence only when referring to treatment and prevention of TMD. The majority of orthodontists believe that, despite scientific evidence, orthodontic treatment can cause TMD. .


INTRODUÇÃO: o consenso sobre a relação entre DTM e tratamento ortodôntico foi de uma associação de causa e efeito à ideia de que não há evidências confiáveis que suportem essa afirmação. OBJETIVO: avaliar as crenças, sem considerar as evidências, de ortodontistas brasileiros sobre a relação entre DTM e tratamento ortodôntico com relação ao tratamento, prevenção e etiologia da DTM. MÉTODOS: um questionário sobre a relação entre DTM e tratamento ortodôntico foi preparado e enviado a ortodontistas brasileiros por meio de e-mail e mídias sociais. As respostas foram analisadas por estatística descritiva, e fortes associações entre as variáveis foram verificadas pelo teste χ2. RESULTADOS: a maioria dos ortodontistas acredita que o tratamento ortodôntico não é o melhor tratamento para DTM. Além disso, acreditam que não é a melhor forma para sua prevenção. Também, a maioria dos ortodontistas acredita que o tratamento ortodôntico pode causar sintomas de DTM. CONCLUSÃO: este estudo sugere que as crenças dos ortodontistas sobre a relação entre tratamento ortodôntico e DTM estão de acordo com as evidências científicas apenas quando se trata do tratamento e da prevenção de DTM. A maioria dos ortodontistas acredita que, apesar das evidências científicas, o tratamento ortodôntico pode causar DTM. .


Subject(s)
Humans , Cell Cycle Proteins/metabolism , DNA Replication/genetics , Forkhead Transcription Factors/metabolism , G1 Phase/physiology , Gene Expression Regulation/genetics , Protein Serine-Threonine Kinases/metabolism , Replication Origin/genetics , Signal Transduction/genetics , Blotting, Western , Cell Fractionation , Cell Line , Cell Cycle Proteins/genetics , /metabolism , DNA Primers/genetics , Fluorescent Antibody Technique , Forkhead Transcription Factors/genetics , Immunoblotting , Immunoprecipitation , Intercellular Signaling Peptides and Proteins/metabolism , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins c-myc/metabolism , Reverse Transcriptase Polymerase Chain Reaction , RNA Interference
5.
Dental press j. orthod. (Impr.) ; 20(1): 79-84, Jan-Feb/2015. tab, graf
Article in English | LILACS | ID: lil-741451

ABSTRACT

OBJECTIVE: The aim of the present study was to determine the morphological differences in the base of the skull of individuals with cleft lip and palate and Class III malocclusion in comparison to control groups with Class I and Class III malocclusion. METHODS: A total of 89 individuals (males and females) aged between 5 and 27 years old (Class I, n = 32; Class III, n = 29; and Class III individuals with unilateral cleft lip and palate, n = 28) attending PUC-MG Dental Center and Cleft Lip/Palate Care Center of Baleia Hospital and PUC-MG (CENTRARE) were selected. Linear and angular measurements of the base of the skull, maxilla and mandible were performed and assessed by a single calibrated examiner by means of cephalometric radiographs. Statistical analysis involved ANCOVA and Bonferroni correction. RESULTS: No significant differences with regard to the base of the skull were found between the control group (Class I) and individuals with cleft lip and palate (P > 0.017). The cleft lip/palate group differed from the Class III group only with regard to CI.Sp.Ba (P = 0.015). Individuals with cleft lip and palate had a significantly shorter maxillary length (Co-A) in comparison to the control group (P < 0.001). No significant differences were found in the mandible (Co-Gn) of the control group and individuals with cleft lip and palate (P = 1.000). CONCLUSION: The present findings suggest that there are no significant differences in the base of the skull of individuals Class I or Class III and individuals with cleft lip and palate and Class III malocclusion. .


OBJETIVO: o objetivo do presente estudo foi determinar diferenças morfológicas da base do crânio de indivíduos portadores de fissura de lábio e palato e de má oclusão de Classe III, comparado-os com indivíduos controle com má oclusão de Classes I ou III. MÉTODOS: oitenta e nove indivíduos, de ambos os sexos, com idade variando entre 5 e 27 anos, Classe I (n = 32), Classe III não fissurados (n = 29) e Classe III com fissura labiopalatina unilateral (n = 28), oriundos do Centro de Odontologia e Pesquisa da PUC-MG e do Centro de Atendimento de Fissurados do Hospital da Baleia e da PUC-MG (CENTRARE), foram selecionados. Medições lineares e angulares da base do crânio, maxila e mandíbula foram realizadas e avaliadas por um único examinador calibrado, por meio de radiografias cefalométricas. Foram utilizados os testes ANCOVA e correção de Bonferroni para a análise estatística dos dados. RESULTADOS: com relação à base do crânio, os resultados não indicaram diferença estatística entre indivíduos controle (Classe I) e os indivíduos com fissuras (p > 0,017). O grupo com fissura foi diferente do grupo Classe III somente em relação à medida CI.Sp.Ba (p = 0,015). O comprimento maxilar (Co-A) apresentou diferença estatisticamente significativa na comparação entre o grupo controle (Classe I) e o grupo com fissuras (p < 0,001), sendo que os fissurados apresentaram uma maxila menor. Não foram encontradas diferenças na mandíbula (Co-Gn) entre indivíduos do grupo controle (Classe I) e indivíduos fissurados (p = 1,000). CONCLUSÃO: os resultados sugerem que não houve diferença estatisticamente significativa na base do crânio entre indivíduos Classe I e III e indivíduos com fissuras de lábio e palato com má oclusão de Classe III. .


Subject(s)
Animals , Female , Cardiomegaly/metabolism , Cardiomegaly/pathology , Fetal Heart/metabolism , Fetal Heart/pathology , Maternal Nutritional Physiological Phenomena , Overnutrition/metabolism , Overnutrition/pathology , Biomarkers/metabolism , Calcineurin/metabolism , Cardiovascular Diseases/epidemiology , Extracellular Space , Fascia/pathology , Forkhead Transcription Factors/metabolism , Gene Expression Regulation, Developmental , Myofibrils/pathology , NFATC Transcription Factors/metabolism , Natriuretic Peptides/genetics , Natriuretic Peptides/metabolism , Phosphorylation , RNA, Messenger/metabolism , Sheep, Domestic , TOR Serine-Threonine Kinases/metabolism
7.
Gut and Liver ; : 370-380, 2015.
Article in English | WPRIM | ID: wpr-203889

ABSTRACT

BACKGROUND/AIMS: This study investigated the expression of T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3), human beta-defensin (HBD)-2, forkhead box protein 3 (FOXP3), and the frequency of CD4+ CD25+ FOXP3+ regulatory T cells (Tregs) in children with Crohn's disease (CD) during infliximab therapy. METHODS: We enrolled 20 CD patients who received infliximab treatment for 1 year. Peripheral blood and colonic mucosal specimens were collected from all CD patients and from healthy control individuals. RESULTS: A significant difference in TIM-3 mRNA expression was evident in peripheral blood mononuclear cells and colonic mucosa between CD patients before infliximab therapy and the healthy controls (p<0.001 and p=0.005, respectively). A significant difference in HBD-2 mRNA expression was found in colonic mucosa between CD patients before infliximab therapy and the healthy controls (p=0.013). In the active phase of CD, at baseline, the median percentage of T cells that were CD25+ FOXP3+ was 1.5% (range, 0.32% to 3.49%), which increased after inflixmab treatment for 1 year to 2.2% (range, 0.54% to 5.02%) (p=0.008). CONCLUSIONS: Our study suggests that both the adaptive and innate immune systems are closely linked to each other in CD pathogenesis. And the results of our study indicate that it could be a useful therapeutic tool, where restoration of TIM-3, HBD-2 and the function of Tregs may repair the dysfunctional immunoregulation in CD.


Subject(s)
Adolescent , Case-Control Studies , Colon/immunology , Crohn Disease/drug therapy , Female , Forkhead Transcription Factors/metabolism , Gastrointestinal Agents/therapeutic use , Humans , Infliximab/therapeutic use , Intestinal Mucosa/immunology , Leukocytes, Mononuclear/metabolism , Male , Membrane Proteins/metabolism , T-Lymphocytes, Regulatory/immunology , beta-Defensins/metabolism
8.
Yonsei Medical Journal ; : 1590-1596, 2015.
Article in English | WPRIM | ID: wpr-177065

ABSTRACT

PURPOSE: Foxo3 in female reproduction has been reported to regulate proliferation of granulose cells that form follicles. There are no reports so far that discuss on the role of Foxo3 in males. This study was designed to outline the role of Foxo3 in the testes. MATERIALS AND METHODS: Testes from mice at birth to postpartum week (PPW) 5 were isolated and examined for the expression of Foxo3 using immunostaining. To elucidate role of Foxo3 in Leydig cells, R2C cells were treated with luteinizing hormone (LH) and the phosphorylation of Foxo3. Testosterone and steroidogenic acute regulatory (StAR) protein levels were measured after constitutive active [triple mutant (TM)] human FOXO3 adenovirus was transduced and StAR promoter assay was performed. RESULTS: Foxo3 expression in the testicles started from birth and lasted until PPW 3. After PPW 3, most Foxo3 expression occurred in the nuclei of Leydig cells; however, at PPW 5, Foxo3 was expressed in both the nucleus and cytoplasm. When R2C cells were treated with luteinizing hormone, Foxo3 phosphorylation levels by AKT increased. After blocking the PI3K pathway, LH-induced phosphorylated Foxo3 levels decreased, indicating that LH signaling regulates Foxo3 localization. When active FOXO3-TM adenovirus was introduced into a Leydig tumor cell line, the concentrations of testosterone and StAR protein decreased. When FOXO3 and a StAR promoter vector were co-transfected into HEK293 cells for a reporter assay, FOXO3 inhibited the StAR promoter. CONCLUSION: FOXO3 affects testosterone synthesis by inhibiting the formation of StAR protein. LH hormone, meanwhile, influences Foxo3 localization, mediating its function.


Subject(s)
Animals , Cellular Senescence/physiology , Cell Nucleus/metabolism , Cytoplasm/metabolism , Forkhead Transcription Factors/metabolism , HEK293 Cells , Humans , Leydig Cells/drug effects , Luteinizing Hormone/blood , Male , Mice , Phosphatidylinositol 3-Kinases , Phosphoproteins/metabolism , Phosphorylation , Signal Transduction/drug effects , Testosterone/blood
9.
Article in English | WPRIM | ID: wpr-35685

ABSTRACT

This study investigated whether tempol, an anti-oxidant, protects against renal injury by modulating phosphatidylinositol 3-kinase (PI3K)-Akt-Forkhead homeobox O (FoxO) signaling. Mice received unilateral ureteral obstruction (UUO) surgery with or without administration of tempol. We evaluated renal damage, oxidative stress and the expression of PI3K, Akt, FoxO3a and their target molecules including manganese superoxide dismutase (MnSOD), catalase, Bax, and Bcl-2 on day 3 and day 7 after UUO. Tubulointerstitial fibrosis, collagen deposition, alpha-smooth muscle actin-positive area, and F4/80-positive macrophage infiltration were significantly lower in tempol-treated mice compared with control mice. The expression of PI3K, phosphorylated Akt, and phosphorylated FoxO3a markedly decreased in tempol-treated mice compared with control mice. Tempol prominently increased the expressions of MnSOD and catalase, and decreased the production of hydrogen peroxide and lipid peroxidation in the obstructed kidneys. Significantly less apoptosis, a lower ratio of Bax to Bcl-2 expression and fewer apoptotic cells in TUNEL staining, and decreased expression of transforming growth factor-beta1 were observed in the obstructed kidneys from tempol-treated mice compared with those from control mice. Tempol attenuates oxidative stress, inflammation, and fibrosis in the obstructed kidneys of UUO mice, and the modulation of PI3K-Akt-FoxO3a signaling may be involved in this pathogenesis.


Subject(s)
Animals , Antioxidants/pharmacology , Collagen/metabolism , Cyclic N-Oxides/pharmacology , Fibrosis , Forkhead Transcription Factors/metabolism , Hydrogen Peroxide/metabolism , Kidney Diseases/drug therapy , Lipid Peroxidation , Male , Mice , Mice, Inbred C57BL , Oxidative Stress/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Severity of Illness Index , Signal Transduction/drug effects , Spin Labels , Superoxide Dismutase/metabolism , Ureteral Obstruction/complications
10.
Article in Korean | WPRIM | ID: wpr-46505

ABSTRACT

BACKGROUND/AIMS: The unique role of enzyme 5-lipoxygenase (5-LO) in the production of leukotrienes makes it a therapeutic target for inflammatory bowel disease (IBD). The aim of this study was to evaluate the effects of B-98, a newly synthesized benzoxazole derivatives and a novel 5-LO inhibitor, in a mouse model of IBD induced by dextran sulfate sodium (DSS). METHODS: C57BL/6 mice were randomly assigned to four groups: normal control, DSS colitis (DSS+saline), low dose B-98 (DSS+B-98 20 mg/kg) and high dose B-98 (DSS+B-98 100 mg/kg). B-98 was administered with 3% DSS intraperitoneally. The severity of the colitis was assessed via the disease activity index (DAI), colon length, and histopathologic grading. The production of inflammatory cytokines interleukin (IL)-6 was determined by RT-PCR. Th cells were examined for the proportion of Th1 cell, Th2 cell, Th9 cell, Th17 cell and Treg cell using intracellular cytometry. RESULTS: The B-98 group showed lower DAI, less shortening of the colon length and lower histopathologic grading compared with the DSS colitis group (p<0.01). The expression of IL-6 in colonic tissue was significantly lower in the B-98 groups than the DSS colitis group (p<0.05). The cellular profiles revealed that the Th1, Th9 and Th17 cells were increased in the DSS colitis group compared to the B-98 group (p<0.05). CONCLUSIONS: Our results suggest that acute intestinal inflammation is reduced in the group treated with B-98 by Th1, Th9 and Th17 involved cellular immunity.


Subject(s)
Acute Disease , Animals , Arachidonate 5-Lipoxygenase/chemistry , Benzoxazoles/chemistry , Colitis/chemically induced , Colon/drug effects , Dextran Sulfate/toxicity , Disease Models, Animal , Forkhead Transcription Factors/metabolism , Injections, Intraperitoneal , Interleukin-6/genetics , Lipoxygenase Inhibitors/chemistry , Male , Mice , Mice, Inbred C57BL , Severity of Illness Index , T-Lymphocytes/classification
11.
Yonsei Medical Journal ; : 1422-1429, 2013.
Article in English | WPRIM | ID: wpr-100957

ABSTRACT

PURPOSE: Recently, Forkhead box M1 (FoxM1) was reported to be correlated with lung maturation and expression of surfactant proteins (SPs) in mice models. However, no study has been conducted in rabbit lungs despite their high homology with human lungs. Thus, we attempted to investigate serial changes in the expressions of FoxM1 and SP-A/B throughout lung maturation in rabbit fetuses. MATERIALS AND METHODS: Pregnant New Zealand White rabbits were grouped according to gestational age from 5 days before to 2 days after the day of expected full term delivery (F5, F4, F3, F2, F1, F0, P1, and P2). A total of 64 fetuses were enrolled after Cesarean sections. The expressions of mRNA and proteins of FoxM1 and SP-A/B in fetal lung tissue were tested by quantitative reverse-transcriptase real-time PCR and Western blot. Furthermore, their correlations were analyzed. RESULTS: The mRNA expression of SP-A/B showed an increasing tendency positively correlated with gestational age, while the expression of FoxM1 mRNA and protein decreased from F5 to F0. A significant negative correlation was found between the expression levels of FoxM1 and SP-A/B (SP-A: R=-0.517, p=0.001; SP-B: R=-0.615, p<0.001). CONCLUSION: Preterm rabbits demonstrated high expression of FoxM1 mRNA and protein in the lungs compared to full term rabbits. Also, the expression of SP-A/B was inversely related with serial changes in FoxM1 expression. This is the first report to suggest an association between FoxM1 and expression of SP-A/B and lung maturation in preterm rabbits.


Subject(s)
Animals , Blotting, Western , Female , Fetus/metabolism , Forkhead Transcription Factors/metabolism , Lung/metabolism , Pregnancy , Pulmonary Surfactant-Associated Protein A/genetics , Rabbits
12.
Indian J Biochem Biophys ; 2012 Feb; 49(1): 25-35
Article in English | IMSEAR | ID: sea-140215

ABSTRACT

Psoriasis vulgaris (PV) is a common autoimmune disease that involves the dysfunction of CD4+CD25+ regulatory T cells. FOXP3 is a key transcription factor in the development and function of CD4+CD25+ regulatory T cells. Previous studies have demonstrated a genetic association between the FOXP3 gene and some autoimmune diseases. To elucidate the association between the FOXP3 gene and the risk of PV, 408 patients diagnosed with PV and 363 age and sex-matched healthy controls from a cohort of the Chinese majority Han population were recruited. Four single nucleotide polymorphisms (rs2232365, rs3761547, rs3761548 and rs3761549) of the FOXP3 gene were analyzed using the polymerase chain reaction and ligase detection reaction. The major allele of three single nucleotide polymorphisms (SNPs — rs2232365 A, rs3761547 A and rs3761549 C) were associated with an increased risk of PV in a clinical subgroup of female patients, who were less than 40 yrs of age, had a family history of the disease and did not have disease complications (p < 0.05 for all parameters). The haplotype was structured between rs3761547 and rs3761549. An increased risk of PV was observed in haplotype A/A-T/T (p = 0.0055; adjusted OR = 3.188; 95% CI = 0.4354-23.34) and A/G-C/C (p = 0.0082; adjusted OR = 1.288; 95% CI = 0.1529-10.85) between rs3761547 and rs3761549. A synergistic effect was found among the three SNPs. Subjects with the rs2232365AA- rs3761547 AG + GG genotype were more susceptible to PV (p = 0.0393; OR = 2.90; 95% CI = 1.05-7.97). No correlation was found between rs3761548 and the onset of PV. Therefore, the FOXP3 polymorphisms appear to contribute to the risk of psoriasis among the Chinese majority Han population. These findings may aid in our understanding of the pathogenesis of psoriasis


Subject(s)
Adult , Asians/genetics , China/epidemiology , Cohort Studies , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Genetic Predisposition to Disease , Genotype , Haplotypes/genetics , Humans , Inteins/genetics , Polymorphism, Single Nucleotide/genetics , Psoriasis/epidemiology , Psoriasis/genetics , Risk
13.
Article in English | WPRIM | ID: wpr-154191

ABSTRACT

Recently, subpopulations of regulatory T (Treg) cells, resting Treg (rTreg) and activated Treg (aTreg), have been discovered. The authors investigated the relationship between the change of Treg, aTreg and rTreg and autoimmune diseases. Treg cells and those subpopulations were analyzed by using the human regulatory T cell staining kit and CD45RA surface marker for 42 rheumatoid arthritis (RA), 13 systemic lupus sclerosis (SLE), 7 Behcet's disease (BD), and 22 healthy controls. The proportion of Treg cells was significantly lower in RA (3.8% +/- 1.0%) (P < 0.001) and BD (3.3% +/- 0.5%) (P < 0.01) compared to healthy controls (5.0% +/- 1.3%). The proportion of aTreg cells was also significantly lower in RA (0.4% +/- 0.2%) (P = 0.008) and BD (0.3% +/- 0.1%) (P = 0.013) compared to healthy controls (0.6% +/- 0.3%). The rTreg cells showed no significant differences. The ratio of aTreg to rTreg was lower in RA patients (0.4% +/- 0.2%) than that in healthy controls (0.7% +/- 0.4%) (P = 0.002). This study suggests that the decrement of aTreg not rTreg cells contributes the decrement of total Treg cells in peripheral blood of RA and BD autoimmune diseases. Detailed analysis of Treg subpopulations would be more informative than total Treg cells in investigating mechanism of autoimmune disease.


Subject(s)
Adult , Aged , CD4 Antigens/metabolism , Leukocyte Common Antigens/metabolism , Arthritis, Rheumatoid/immunology , Behcet Syndrome/immunology , Female , Forkhead Transcription Factors/metabolism , Humans , Interleukin-2 Receptor alpha Subunit/metabolism , Leukocyte Count , Lupus Erythematosus, Systemic/immunology , Male , Middle Aged , T-Lymphocytes, Regulatory/cytology
14.
Article in English | WPRIM | ID: wpr-164056

ABSTRACT

BACKGROUND: CD4+CD25+ regulatory T-cells (Tregs) play a critical role in immune responses. We explored the status of Tregs in neoplastic and autoimmune hematologic diseases. We also evaluated the technical aspects of Treg measurement in terms of sample type and detection markers. METHODS: A total of 68 subjects were enrolled: 11 with AML, 8 with MDS, 10 with autoimmune diseases, and 39 controls. Tregs were analyzed in peripheral blood (PB) and bone marrow (BM) samples from each subject. Flow cytometry and the Human Regulatory T cell Staining Kit (eBioscience, USA) for CD4, CD25, and FoxP3 (forkhead box P3) were used. RESULTS: The CD4+CD25high/CD4 and CD4+CD25highFoxP3+/CD4 populations were significantly correlated (P<0.0001). The AML and high-risk MDS groups had significantly larger CD4+CD25high/CD4 and CD4+CD25highFoxP3+/CD4 populations in PB than the autoimmune (P=0.007 and 0.012, respectively) and control groups (P=0.004 and 0.006, respectively). Comparable findings were observed in BM. The CD4+CD25highFoxP3+/CD4 population was significantly larger in PB than in BM (P=0.0003). CONCLUSIONS: This study provides comparison data for Tregs in AML, MDS, and autoimmune hematologic diseases, and would be helpful for understanding the different immunologic bases of various hematologic diseases. Treg measurement using CD4, CD25, and/or FoxP3 in PB rather than in BM seems to be practical for routine hematologic purposes. Large-scale analysis of the diagnostic role of Treg measurement is needed.


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Autoimmune Diseases/diagnosis , Bone Marrow Cells/cytology , Female , Flow Cytometry , Forkhead Transcription Factors/metabolism , Hematologic Diseases/diagnosis , Humans , Interleukin-2 Receptor alpha Subunit/metabolism , Leukemia, Myeloid, Acute/diagnosis , Leukocytes, Mononuclear/cytology , Male , Middle Aged , Myelodysplastic Syndromes/diagnosis , T-Lymphocytes, Regulatory/immunology
15.
Article in English | WPRIM | ID: wpr-155753

ABSTRACT

The aim of this study was to evaluate whether the Th17 and Treg cell infiltration into allograft tissue is associated with the severity of allograft dysfunction and tissue injury in acute T cell-mediated rejection (ATCMR). Seventy-one allograft tissues with biopsy-proven ATCMR were included. The biopsy specimens were immunostained for FOXP3 and IL-17. The allograft function was assessed at biopsy by measuring serum creatinine (Scr) concentration, and by applying the modified diet in renal disease (MDRD) formula, which provides the estimated glomerular filtration rate (eGFR). The severity of allograft tissue injury was assessed by calculating tissue injury scores using the Banff classification. The average numbers of infiltrating Treg and Th17 cells were 11.6 +/- 12.2 cells/mm2 and 5.6 +/- 8.0 cells/mm2, respectively. The average Treg/Th17 ratio was 5.6 +/- 8.2. The Treg/Th17 ratio was significantly associated with allograft function (Scr and MDRD eGFR) and with the severity of interstitial injury and tubular injury (P < 0.05, all parameters). In separate analyses of the number of infiltrating Treg and Th17 cells, Th17 cell infiltration was significantly associated with allograft function and the severity of tissue injury. By contrast, Treg cell infiltration was not significantly associated with allograft dysfunction or the severity of tissue injury. The results of this study show that higher infiltration of Th17 cell compared with Treg cell is significantly associated with the severity of allograft dysfunction and tissue injury.


Subject(s)
Acute Disease , Creatinine/metabolism , Forkhead Transcription Factors/metabolism , Graft Rejection/etiology , Humans , Immunoenzyme Techniques , Interleukin-17/metabolism , Kidney Transplantation/adverse effects , Retrospective Studies , T-Lymphocytes, Regulatory/immunology , Th17 Cells/immunology , Transplantation, Homologous
16.
Braz. j. med. biol. res ; 43(11): 1109-1115, Nov. 2010. ilus, tab
Article in English | LILACS | ID: lil-564141

ABSTRACT

HTLV-1 Tax expression exerts an inhibitory effect on the Foxp3 transcription factor in CD4+CD25+ T-regulatory cells (Treg). For a better understanding of the role of Tax mRNA in the gene expression of cellular markers we measured Tax, Foxp3, CTLA-4, GITR, TGF-β, and IL-10 mRNA in Treg cells of 50 patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP; 27 women and 23 men; mean age: 56.7 years). The control group consisted of 23 non-infected subjects (12 women and 11 men) with a mean age of 51.3 years. Real-time PCR was used to measure mRNA of Tax proteins and several cellular markers of Treg function. Determinations revealed a high level of Tax mRNA in HAM/TSP (124.35 copies/100 CD4+CD25+ T cells). Foxp3, GITR, and CTLA-4 mRNA levels were lower in HAM/TSP patients (mean ± SD, 22.07 ± 0.78, 9.63 ± 0.36, and 4.54 ± 0.39, respectively) than in non-infected controls (47.15 ± 12.94, 22.14 ± 1.91, and 21.07 ± 2.31). Both groups had similar levels of TGF-β and IL-10. An inverse relationship was found between Tax levels and Foxp3, CTLA-4, and GITR levels. Conversely, there was a direct correlation between levels of Foxp3, GITR, and CTLA-4. Disease severity and evolution time did not correlate with Tax or Foxp3 levels. The present results suggest that Tax and Foxp3 mRNA vary with the same degree of disease severity in HAM/TSP patients. Tax fluctuations may affect CTLA-4 and GITR expression via the Foxp3 pathway, causing virus-induced dysfunction of CD4+CD25+ T cells in HAM/TSP patients.


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , /metabolism , Forkhead Transcription Factors/metabolism , Gene Products, tax/metabolism , Glucocorticoid-Induced TNFR-Related Protein/metabolism , Human T-lymphotropic virus 1 , Paraparesis, Tropical Spastic/blood , Biomarkers/blood , Biomarkers/metabolism , Case-Control Studies , /blood , Forkhead Transcription Factors/blood , Gene Products, tax/blood , Glucocorticoid-Induced TNFR-Related Protein/blood , Paraparesis, Tropical Spastic/metabolism , Real-Time Polymerase Chain Reaction , RNA, Messenger/blood , Severity of Illness Index , Transforming Growth Factor beta/blood , Transforming Growth Factor beta/metabolism
17.
Braz. j. med. biol. res ; 42(10): 935-941, Oct. 2009. ilus, tab
Article in English | LILACS | ID: lil-526197

ABSTRACT

A low-protein diet leads to functional and structural pancreatic islet alterations, including islet hypotrophy. Insulin-signaling pathways are involved in several adaptive responses by pancreatic islets. We determined the levels of some insulin-signaling proteins related to pancreatic islet function and growth in malnourished rats. Adult male Wistar rats (N = 20 per group) were fed a 17 percent protein (normal-protein diet; NP) or 6 percent protein (low-protein diet; LP), for 8 weeks. At the end of this period, blood glucose and serum insulin and albumin levels were measured. The morphometric parameters of the endocrine pancreas and the content of some proteins in islet lysates were determined. The β-cell mass was significantly reduced (≅65 percent) in normoglycemic but hypoinsulinemic LP rats compared to NP rats. Associated with these alterations, a significant 30 percent reduction in insulin receptor substrate-1 and a 70 percent increase in insulin receptor substrate-2 protein content were observed in LP islets compared to NP islets. The phosphorylated serine-threonine protein kinase (pAkt)/Akt protein ratio was similar in LP and NP islets. The phosphorylated forkhead-O1 (pFoxO1)/FoxO1 protein ratio was decreased by 43 percent in LP islets compared to NP islets (P < 0.05). Finally, the ratio of phosphorylated-extracellular signal-related kinase 1/2 (pErk1/2) to total Erk1/2 protein levels was decreased by 71 percent in LP islets compared to NP islets (P < 0.05). Therefore, the reduced β-cell mass observed in LP rats is associated with the reduction of phosphorylation in mitogenic-related signals, FoxO1 and Erk proteins. The cause/effect basis of this association remains to be determined.


Subject(s)
Animals , Male , Rats , Forkhead Transcription Factors/metabolism , Insulin-Secreting Cells/pathology , /metabolism , Nerve Tissue Proteins/metabolism , Protein-Energy Malnutrition , Diet, Protein-Restricted , Phosphorylation , Protein-Energy Malnutrition/metabolism , Protein-Energy Malnutrition/pathology , Rats, Wistar
18.
Article in English | WPRIM | ID: wpr-76613

ABSTRACT

Resveratrol is a polyphenolic compound in red wine that has anti-oxidant and cardioprotective effects in animal models. Reactive oxygen species (ROS) and monocyte chemotactic protein-1 (MCP-1) play key roles in foam cell formation and atherosclerosis. We studied LPS-mediated foam cell formation and the effect of resveratrol. Resveratrol pretreatment strongly suppressed LPS-induced foam cell formation. To determine if resveratrol affected the expression of genes that control ROS generation in macrophages, NADPH oxidase 1 (Nox1) was measured. Resveratrol treatment of macrophages inhibited LPS-induced Nox1 expression as well as ROS generation, and also suppressed LPS-induced MCP-1 mRNA and protein expression. We investigated the upstream targets of Nox1 and MCP-1 expression and found that Akt-forkhead transcription factors of the O class (FoxO3a) is an important signaling pathway that regulates both genes. These inhibitory effects of resveratrol on Nox1 expression and MCP-1 production may target to the Akt and FoxO3a signaling pathways.


Subject(s)
Antioxidants/pharmacology , Cells, Cultured , Chemokine CCL2/genetics , Enzyme Activation/drug effects , Foam Cells/drug effects , Forkhead Transcription Factors/metabolism , Humans , Lipopolysaccharides/pharmacology , NADH, NADPH Oxidoreductases/genetics , Proto-Oncogene Proteins c-akt/metabolism , RNA, Messenger/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction , Stilbenes/pharmacology
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