RESUMO
Objective: A consistent body of research has confirmed that patients with major depressive disorder (MDD) have increased concentrations of pro-inflammatory cytokines, including IL-6, TNF-α, IL-1β, the soluble IL-2 receptor, and C-reactive protein, compared to controls; however, there is limited information on IL-17A in MDD. Moreover, information about IL-17A in older populations, i.e., patients with late-life depression (LLD), is conspicuously missing from the literature. The purpose of this study was to investigate the role of IL-17A in LLD. Methods: A convenience sample of 129 individuals, 74 with LLD and 55 non-depressed controls, were enrolled in this study. The Mann-Whitney U test was used to compare plasma IL-17A levels between LLD and controls subjects, and Spearman's rank order correlation was used to investigate correlation of these levels with clinical, neuropsychological, and cognitive assessments. Results: Plasma IL-17A levels were not statistically different between LLD patients and controls (p = 0.94). Among all subjects (LLD + control), plasma IL-17A did not correlate significantly with depressive symptoms (rho = -0.009, p = 0.92) but a significant correlation was observed with cognitive assessments (rho = 0.22, p = 0.01). Conclusion: Our findings do not support an association between plasma IL-17A levels and LLD. Nevertheless, IL-17A may be associated with cognitive impairment in LLD patients. If this finding is confirmed in future longitudinal studies, modulation of the T-helper 17 cell (Th17) immune response may be a treatment target for cognitive impairment in this population.
Assuntos
Humanos , Masculino , Feminino , Idoso , Interleucina-17/sangue , Transtorno Depressivo Maior/sangue , Biomarcadores/sangue , Estudos de Casos e ControlesRESUMO
The aim of the present study is to experimentally measure the volume and composition of biogas produced from the anaerobic biodigestion of laying-hen manure from poultry farms in Itanhandu-MG, Brazil, so that the biogas can be used to generate energy. Two experiments (E1 and E2) were used to characterise the biogas quantities and compositions at room temperature and at a controlled temperature of 36 °C, respectively. The biogas production and calculated net power from the exploitation of biogas energy were compared with the results obtained from methods proposed by the Environmental Company of the State of São Paulo (CETESB, an acronym in Portuguese) using the 'Biogas: Generation and energy use - effluent and rural waste' software 1.0, Brasília-DF, Brazil. In addition, after a time equal to the hydraulic retention time subsequent to biodigester loading, the parameters were analysed and correlated with the organic matter content in the substrates. The effluents were subsequently compared with verify the degree of degradability. The biogas volumes were estimated to be 0.143 m3 kg VTS-1 for E1 and 0.283 m3 kg VTS-1 for E2. If the poultry farm considered in this case study uses manure to generate energy, then the estimated energy generation based on the data from experiments E1 and E2 will result in net energy values of 683 MW h y-1 and 27,160 MW h y-1, given 620 MW h y-1 for sludge heating in E2. The energy production values from the simulations of the E1 and E2 experiments did not demonstrate economic viability under the studied conditions.
Assuntos
Biocombustíveis , Esterco , Aves Domésticas , Anaerobiose , Animais , Reatores Biológicos , Brasil , Galinhas , Feminino , MetanoRESUMO
OBJECTIVE: A consistent body of research has confirmed that patients with major depressive disorder (MDD) have increased concentrations of pro-inflammatory cytokines, including IL-6, TNF-α, IL-1ß, the soluble IL-2 receptor, and C-reactive protein, compared to controls; however, there is limited information on IL-17A in MDD. Moreover, information about IL-17A in older populations, i.e., patients with late-life depression (LLD), is conspicuously missing from the literature. The purpose of this study was to investigate the role of IL-17A in LLD. METHODS: A convenience sample of 129 individuals, 74 with LLD and 55 non-depressed controls, were enrolled in this study. The Mann-Whitney U test was used to compare plasma IL-17A levels between LLD and controls subjects, and Spearman's rank order correlation was used to investigate correlation of these levels with clinical, neuropsychological, and cognitive assessments. RESULTS: Plasma IL-17A levels were not statistically different between LLD patients and controls (p = 0.94). Among all subjects (LLD + control), plasma IL-17A did not correlate significantly with depressive symptoms (rho = -0.009, p = 0.92) but a significant correlation was observed with cognitive assessments (rho = 0.22, p = 0.01). CONCLUSION: Our findings do not support an association between plasma IL-17A levels and LLD. Nevertheless, IL-17A may be associated with cognitive impairment in LLD patients. If this finding is confirmed in future longitudinal studies, modulation of the T-helper 17 cell (Th17) immune response may be a treatment target for cognitive impairment in this population.
Assuntos
Transtorno Depressivo Maior/sangue , Interleucina-17/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , MasculinoRESUMO
Tumors develop numerous strategies to fine-tune inflammation and avoid detection and eradication by the immune system. The identification of mechanisms leading to local immune dysregulation is critical to improve cancer therapy. We here demonstrate that Interleukin-1 receptor 8 (IL-1R8 - previously known as SIGIRR/TIR8), a negative regulator of Toll-Like and Interleukin-1 Receptor family signaling, is up-regulated during breast epithelial cell transformation and in primary breast tumors. IL-1R8 expression in transformed breast epithelial cells reduced IL-1-dependent NF-κB activation and production of pro-inflammatory cytokines, inhibited NK cell activation and favored M2-like macrophage polarization. In a murine breast cancer model (MMTV-neu), IL-1R8-deficiency reduced tumor growth and metastasis and was associated with increased mobilization and activation of immune cells, such as NK cells and CD8+ T cells. Finally, immune-gene signature analysis in clinical specimens revealed that high IL-1R8 expression is associated with impaired innate immune sensing and T-cell exclusion from the tumor microenvironment. Our results indicate that high IL-1R8 expression acts as a novel immunomodulatory mechanism leading to dysregulated immunity with important implications for breast cancer immunotherapy.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Regulação Neoplásica da Expressão Gênica , Imunidade/genética , Receptores de Interleucina-1/genética , Animais , Neoplasias da Mama/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/imunologia , Citocinas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Humanos , Imunidade Inata/genética , Imunomodulação , Mediadores da Inflamação/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Camundongos , Camundongos Knockout , NF-kappa B/metabolismo , Evasão Tumoral/genéticaRESUMO
BACKGROUND: Previous studies have shown that acupuncture and electroacupuncture (EA) are effective in the treatment of patients with low back pain. However, there is little evidence to support the use of one intervention over the other. The aim of this study is to compare the effect of acupuncture and electroacupuncture in the treatment of pain and disability in patients with chronic nonspecific low back pain. METHODS/DESIGN: The study design is a randomized controlled trial. Patients with nonspecific chronic low back pain of more than three months duration are recruited at Rehabilitation Center of Taboao da Serra - SP (Brazil). After examination, sixty-six patients will be randomized into one of two groups: acupuncture group (AG) (n = 33) and electroacupuncture group (EG) (n = 33). Interventions will last one hour, and will happen twice a week for 6 weeks. The primary clinical outcomes will be pain intensity as measured and functional disability. SECONDARY OUTCOMES: quality of pain, quality of life. perception of the overall effect, depressive state, flexibility and kinesiophobia. All the outcomes will be assessed will be assessed at baseline, at treatment end, and three months after treatment end. Significance level will be determined at the 5 % level. Results of this trial will help clarify the value of acupuncture and electroacupuncture as a treatment for chronic low back pain and if they are different. DISCUSSION: Results of this trial will help clarify the value of acupuncture needling and electroacupuncture stimulation of specific points on the body as a treatment for chronic low back pain. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02039037 . Register October 30, 2013.
Assuntos
Terapia por Acupuntura/métodos , Dor Crônica/terapia , Eletroacupuntura/métodos , Dor Lombar/terapia , Terapia por Acupuntura/efeitos adversos , Brasil , Dor Crônica/diagnóstico , Dor Crônica/fisiopatologia , Protocolos Clínicos , Avaliação da Deficiência , Eletroacupuntura/efeitos adversos , Humanos , Dor Lombar/diagnóstico , Dor Lombar/fisiopatologia , Medição da Dor , Qualidade de Vida , Projetos de Pesquisa , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
The purpose of the study was to compare hip agonist-antagonist isometric strength ratios between females with patellofemoral pain (PFP) syndrome and pain-free control group. One hundred and twenty females between 15 and 40 years of age (control group: n = 60; PFP group: n = 60) participated in the study. Hip adductor, abductor, medial rotator, lateral rotator, flexor, and extensor isometric strength were measured using a hand-held dynamometer. Comparisons in the hip adductor/abductor and medial/lateral rotator and flexor/extensor strength ratios were made between groups using independent t-tests. Group comparisons also were made between the anteromedial hip complex (adductor, medial rotator, and flexor musculature) and posterolateral hip complex (abductor, lateral rotator, and extensor musculature). On average, the hip adductor/abductor isometric strength ratio in the PFP group was 23% higher when compared with the control group (p = 0.01). The anteromedial/posterolateral complex ratio also was significantly higher in the PFP group (average 8%; p = 0.04). No significant group differences were found for the medial/lateral rotator ratio and flexor/extensor strength ratios. The results of this study demonstrate that females with PFP have altered hip strength ratios when compared with asymptomatic controls. These strength imbalances may explain the tendency of females with PFP to demonstrate kinematic tendencies that increase loading on the patellofemoral joint (i.e., dynamic knee valgus).
Assuntos
Quadril/fisiopatologia , Força Muscular , Músculo Esquelético/fisiopatologia , Síndrome da Dor Patelofemoral/fisiopatologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Contração Isométrica , Adulto JovemRESUMO
Although patterns of somatic alterations have been reported for tumor genomes, little is known on how they compare with alterations present in non-tumor genomes. A comparison of the two would be crucial to better characterize the genetic alterations driving tumorigenesis. We sequenced the genomes of a lymphoblastoid (HCC1954BL) and a breast tumor (HCC1954) cell line derived from the same patient and compared the somatic alterations present in both. The lymphoblastoid genome presents a comparable number and similar spectrum of nucleotide substitutions to that found in the tumor genome. However, a significant difference in the ratio of non-synonymous to synonymous substitutions was observed between both genomes (P = 0.031). Protein-protein interaction analysis revealed that mutations in the tumor genome preferentially affect hub-genes (P = 0.0017) and are co-selected to present synergistic functions (P < 0.0001). KEGG analysis showed that in the tumor genome most mutated genes were organized into signaling pathways related to tumorigenesis. No such organization or synergy was observed in the lymphoblastoid genome. Our results indicate that endogenous mutagens and replication errors can generate the overall number of mutations required to drive tumorigenesis and that it is the combination rather than the frequency of mutations that is crucial to complete tumorigenic transformation.
Assuntos
Neoplasias da Mama/genética , Variação Genética , Genoma Humano , Linhagem Celular Transformada , Linhagem Celular Tumoral , Aberrações Cromossômicas , Feminino , Humanos , Linfócitos , Pessoa de Meia-Idade , Mutação , Mutação Puntual , Mapeamento de Interação de Proteínas , Análise de Sequência de DNARESUMO
Serial Analysis of Gene Expression (SAGE) and Massively Parallel Signature Sequencing (MPSS) are powerful techniques for gene expression analysis. A crucial step in analyzing SAGE and MPSS data is the assignment of experimentally obtained tags to a known transcript. However, tag to transcript assignment is not a straightforward process since alternative tags for a given transcript can also be experimentally obtained. Here, we have evaluated the impact of Single Nucleotide Polymorphisms (SNPs) on the generation of alternative SAGE and MPSS tags. This was achieved through the construction of a reference database of SNP-associated alternative tags, which has been integrated with SAGE Genie. A total of 2020 SNP-associated alternative tags were catalogued in our reference database and at least one SNP-associated alternative tag was observed for approximately 8.6% of all known human genes. A significant fraction (61.9%) of these alternative tags matched a list of experimentally obtained tags, validating their existence. In addition, the origin of four out of five SNP-associated alternative MPSS tags was experimentally confirmed through the use of the GLGI-MPSS protocol (Generation of Long cDNA fragments for Gene Identification). The availability of our SNP-associated alternative tag database will certainly improve the interpretation of SAGE and MPSS experiments.
Assuntos
Perfilação da Expressão Gênica/métodos , Polimorfismo de Nucleotídeo Único , Enzimas de Restrição do DNA/metabolismo , Bases de Dados Genéticas , Humanos , Dados de Sequência Molecular , RNA Mensageiro/química , Análise de Sequência de RNA , Sitios de Sequências RotuladasRESUMO
Massively Parallel Signature Sequencing (MPSS) is a powerful technique for genome-wide gene expression analysis, which, similar to SAGE, relies on the production of short tags proximal to the 3'end of transcripts. A single MPSS experiment can generate over 10(7) tags, providing a 10-fold coverage of the transcripts expressed in a human cell. A significant fraction of MPSS tags cannot be assigned to known transcripts (orphan tags) and are likely to be derived from transcripts expressed at very low levels (approximately 1 copy per cell). In order to explore the potential of MPSS for the characterization of the human transcriptome, we have adapted the GLGI protocol (Generation of Longer cDNA fragments from SAGE tags for Gene Identification) to convert MPSS tags into their corresponding 3' cDNA fragments. GLGI-MPSS was applied to 83 orphan tags and 41 cDNA fragments were obtained. The analysis of these 41 fragments allowed the identification of novel transcripts, alternative tags generated from polymorphic and alternatively spliced transcripts, as well as the detection of artefactual MPSS tags. A systematic large-scale analysis of the genome by MPSS, in combination with the use of GLGI-MPSS protocol, will certainly provide a complementary approach to generate the complete catalog of human transcripts.
Assuntos
DNA Complementar/biossíntese , Perfilação da Expressão Gênica/métodos , RNA Mensageiro/análise , Processamento Alternativo , Linhagem Celular Tumoral , Biologia Computacional , DNA Complementar/química , Etiquetas de Sequências Expressas , Genoma Humano , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Análise de Sequência de DNARESUMO
We applied a systematic bioinformatics approach, followed by careful manual inspection and experimental validation to identify additional expressed sequences located at the Hereditary Prostate Cancer Region (HPC1) between D1S2818 and D1S1642 on chromosome 1q25. All transcripts already described for the 1q25 region were identified and we were able to define 11 additional expressed sequences within this region (three full-length cDNA clone sequences and eight ESTs), increasing the total number of gene count in this region by 38%. Five out of the 11 expressed sequences identified were shown to be expressed in prostate tissue and thus represent novel disease gene candidates for the HPC1 region. Here, we report a detailed characterization of these five novel disease gene candidates, their expression pattern in various tissues, their genomic organization and functional annotation. Two candidates (RGSL1 and RGSL2) correspond to novel members of the RGS family, which is involved in the regulation of G-protein signaling. RGSL1 and RGLS2 expression was detected by real-time polymerase chain reaction in normal prostate tissue, but could not be detected in prostate tumor cell lines, suggesting they might have a role in prostate cancer.