Inulin Induces IL-10 Secretion and Increased FOXP3 Gene Expression in Human Peripheral Blood Mononuclear Cells

ABSTRACT Inulin is an effective prebiotic and its potential in modulating systemic immunity have been proposed. A subpopulation of T cells, named T regulatory cells (Tregs), expressing the Forkhead boxP3 transcription factor are key mediators of peripheral tolerance and suppress undesirable immune responses. These Tregs can be induced by cytokine transforming growth factor beta (TGF-β) and interleukin 10 (IL-10). This work aimed to evaluate inulin effects on human peripheral blood mononuclear cells (PBMC) in vitro. PBMC were incubated with inulin, and the expression of TGF-(1, FOXP3 and IL-10 was analyzed. Increased supernatant IL-10 levels were observed in PBMC of inulin-treated group (p=0.03). Moreover, FOXP3 gene expression was 7.6 fold higher in inulin-treated PBMC, whereas a trend in TGF-β1 expression was detected (p=0.055). These data suggest that inulin induces an immunosuppressive environment in cultured PBMC by promoting FOXP3 gene expression and IL-10 secretion. These studies offer prospects for further fundamental research in this field.

Involvement of transforming growth factor beta-1 (TGFβ1) cytokine and FOXP3 transcription factor genetic polymorphisms in hematological malignancies

Hematological malignancies (HM) are a group of neoplastic diseases that arise from hematologic cell lineages. Transforming growth factor beta 1 (TGFβ1) is shown to negatively regulate normal and malignant hematopoiesis and, in immunological context, to promote T cell exhaustion and generation of regulatory T cells, which are shown to be deleterious in cancer, by the induction of transcription factor FOXP3 expression. The present study aimed to evaluate TGFB1 exon-1 rs1800470 and FOXP3 intron-1 rs2232365 polymorphisms in relation to HM susceptibility. DNA was extracted from blood samples of 43 HM patients and 142 neoplasia-free individuals and polymorphisms were analyzed by allelic-specific PCR. Association analysis was assessed by the Odds Ratio (OR) with significance level of 5%. Regarding FOXP3 polymorphism, no significant differences were observed in genotype or allele distribution among the patients and controls. However, there was a positive association between TGFB1 TT genotype and HM susceptibility (OR = 4.07; CI95% = 1.94 - 8.52). In the combined analysis, a positive association was also observed for TGFB1 TT and FOXP3 GG genotypes (OR = 4.00; CI95% = 1.54 - 10.41) in relation to HM susceptibility. Our results indicated promising new markers to be further investigated in hematological malignancies.

Análise dos efeitos da epigalocatequina-3-galato (EGCG) de Camelliasinensis (chá verde) em modelo de hepatotoxicidade químicaexperimental induzida pela Dietilnitrosamina (DEN) / Analysis of the effects of epigallocatechin-3-gallate (EGCG) of Camellia sinensis (green tea) in experimental chemical model of hepatotoxicity induced by Diethylnitrosamine (DEN)

A Dietilnitrosamina (DEN), uma substância reconhecidamente hepatotóxica e carcinogênica, foiutilizada na indução da necrose hepática centrolobular em ratos isogênicos Lewis divididos em 5 grupos de 5 animais. O objetivo deste estudo foi avaliar o efeito quimiopreventivo da epigalocatequina-3-galato (EGCG), de Camellia sinensis (chá verde) no tratamento da hepatotoxicidade celular induzida pela DEN. Foi mensurada a concentração sérica da alanina aminotransferase (ALT) e aspartato aminotransferase(AST) dos diferentes grupos experimentais. No ensaio bioquímico para AST e ALT, houve diferença significativa entre os valores médios do grupo controle (163±70,32) comparado ao grupo DEN (1631±1039,44), sugerindo que a DEN influencia na função hepática. Entretanto, não houve diferença significativa entre o grupo DEN e o tratado com epigalocatequina. A lactato desidrogenase (LDH) éconsiderada um marcador bioquímico comum para avaliação da progressão tumoral, e em relação ao LDH, as amostras não apresentaram diferenças significativas entre o grupo DEN (1385,5±43,13) e DEN + EGCG 150mg ou DEN + EGCG 200mg 1537,5±1010,45). Neste trabalho foi demonstrado que a epigalocatequina nas concentrações de 150 e 200 mg/Kg não induziram alterações hepáticas e também não foi possível verificar nenhuma quimioproteção pela EGCG em animais inicialmente tratados comDEN durante 24 horas. Sendo assim, novos experimentos com diferentes concentrações de EGCG sãonecessários para comprovar seu possível efeito quimioprotetor.

Diethylnitrosamine (DEN), a known hepatotoxic and carcinogenic substance, was used in the induction of centrilobular hepatic necrosis in isogenic Lewis rats divided into 5 groups with 5 animals. The aim of this study was to evaluate the chemopreventive effect of epigallocatechin-3-gallate (EGCG)from Camellia sinensis (green tea) in the treatment of cellular hepatotoxicity induced by DEN. It was measured the serum concentration of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of the different experimental groups. In the biochemistry assay for AST and ALT, there was significant difference between median values of control group (163±70.32) compared to DEN group(1631±1039.44), suggesting that DEN influences on hepatic function. However, there was no significant difference between DEN group to that treated with epigallocatechin. Lactate dehydrogenase (LDH) is considered a common biochemical marker for evaluation of tumor progression, and regarding LDH,the samples presented no significant differences between the DEN group (1385.5±43.13) and DEN + EGCG 150mg or DEN + EGCG 200mg (1537.5± 1010.45). In this work it was demonstrated that epigallocatechin concentrations of 150 and 200 mg/kg did not induce liver alterations and though was not verified any chemoprotective effect by EGCG in animals initially treated with DEN for 24 hours. Moreover, new experiments with different concentrations of EGCG are needed to verify its possiblechemoprotector effect.

Hipoplasia septo-óptica-hipofisária em paciente com septo pelúcido normal porém com risco de morte neonatal e a participação potencial do fator de transcrição hipofisário HESX1 / The potential involvement of the pituitary transcription factor HESX1 in the septo-optic-pituitary hypoplasia with normal septum pellucidum but life-threatening neonatal phenotype

A displasia septo-óptica (DSO) é uma síndrome do desenvolvimento considerada heterogênea, pois envolve anomalias da linhamédia do cérebro associadas a disfunções oftalmológicas, neurológicas e do eixo hipotálamo-hipófise. O fenótipo é altamentevariável dificultando a classificação da doença. Relatamos um caso de hipopituitarismo neonatal grave que levou à descobertade malformações cerebrais e hipoplasia do nervo óptico, sendo caracterizada assim a síndrome DSO-like. Mesmo em presençade um septo pelúcido normal e com poucas alterações na ressonância magnética, este paciente apresentou um fenótipo endócrinode alto risco de morte no período neonatal. Mutações genéticas têm sido raramente descritas no HESX1 e estão associadas avárias deficiências hormonais hipofisárias combinadas com a DSO. O gene HESX1 codifica um fator de transcrição pertencenteà classe de genes chamados homeobox. A partir deste gene candidato, foi isolada a região codificadora no DNA para análise porsequenciamento. Este relato de caso com seguimento clínico de 7 anos e estudo genético preliminar apresenta uma discussãoda investigação diagnóstica a partir do quadro inicial, destacando as alterações de neuroimagem encontradas nesta síndrome.

Detection of Lsr2 gene of Mycobacterium leprae in nasal mucus

In the present study, nasal mucus from patients with leprosy were analyzed by PCR using specific primers for Lsr2 gene of Mycobacterium leprae. The presence of Lsr2 gene in the nasal mucus was detected in 25.80% of patients with paucibacillari leprosy, and 23.07% of contacts. Despite the absence of clinical features in the contact individuals, it was possible to detect the presence of Lsr2 gene in the nasal mucus of these individuals. Therefore, PCR detection of M. leprae targeting Lsr2 gene using nasal mucus samples could contribute to early diagnosis of leprosy.

Determinação da lactate desidrogenase (LDH) e do transcrito Bcr-Abl em pacientes com leucemia mielóide crônica / Determination of lactate dehydrogenase (LDH) and Bcr-Abl transcript in the follow-up of patients with chronic myeloid leukemia

Leucemia mieloide crônica (LMC) é uma desordem mieloproliferativa maligna que é originada de célula-tronco pluripotente caracterizada por expansão anormal, maligna de clones de células tronco da medula óssea na circulação. A grande maioria dos pacientes com LMC apresentam transcritos Bcr-Abl. Lactato desidrogenase (LDH), considerado um marcador bioquímico para crescimento tumoral, glicólise anaeróbica, e tem sido considerado um fator de pior prognóstico da LMC. Portanto, este estudo visa avaliar a concentração de LDH no plasma e a detecção do transcrito Bcr-Abl em 22 pacientes com LMC e 56 indivíduos saudáveis. Foram avaliados 22 pacientes com LMC e 56 doadores saudáveis. A concentração de LDH no plasma foi maior nos pacientes com LMC. Todos pacientes com LMC neste estudo estavam em tratamento, mesmo assim quatro pacientes apresentavam o transcrito Bcr-Abl (b3a2) no sangue periférico. Dois dos quatro pacientes com o transcrito b3a2 apresentavam LDH elevado (486 U L-1 e 589 U L-1). Embora o estudo tenha sido realizado com um pequeno número de amostras, é possível sugerir alteração de terapia para os dois pacientes que apresentam o transcrito b3a2 na amostra de sangue periférico com concentração de LDH elevada.

Chronic myeloid leukemia (CML) is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present Bcr-Abl transcripts. Lactate dehydrogenase (LDH) is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the Bcr-Abl transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed with CML and 56 healthy donors. LDH concentration in plasma was higher in patients with CML. All patients with CML in this study were under treatment, but even so four patients had the Bcr-Abl (b3a2) transcript in peripheral blood. Two out of the four patients with b3a2 showed higher LDH (486 U L-1 and 589 U L-1). Thus, although the study was conducted with small numbers of samples, it is possible to suggest therapy alteration for two patients who presented transcript b3a2 in the peripheral blood samples and whose LDH concentration was high, in order to improve the disease

Detection of GBV-C/HGV RNA in cervico-vaginal smears from healthy individuals

The purpose of the present study was to evaluate the sexual transmission of GBV-C/HGV, through RNA detection in cervicovaginal smears. Therefore the GBV-C/HGV RNA in cervicovaginal smears from apparently healthy women was investigated using routine proceedings for prophylactic screening to cervical cancer. GBV-C/HGV RNA was detected by reverse transcriptase and polymerase chain reaction (RT-PCR). Only one woman presented co-infection with human papilloma virus (HPV). The GBV-C/HGV RNA was detected in 13/73 (17.57 percent) healthy women and it's prevalence in participating women between 28-43 years old was 53.85 percent. No association was found with GBV-C/HGV for the age of first sexual intercourse and number of pregnancies. In GBV-C/HGV RNA positive women, 69.23 percent were married. In conclusion, the present findings show that cervical and vaginal specimens could contain the GBV-C/HGV RNA.

O objetivo do presente estudo foi avaliar a transmissão sexual de GBV-C/HBV, através da detecção do RNA viral em raspados cérvico-vaginais. Portanto, a presença do RNA GBV-C/HGV foi investigada em raspados cérvico-vaginais em mulheres aparentemente saudáveis que realizaram exames preventivos para câncer cervical. GBV-C/HGV RNA foi detectado por reação de transcriptase reversa e reação em cadeia da polimerase (RT-PCR). Apenas uma mulher apresentou a co-infecção com o papiloma vírus humano (HPV). O RNA GBV-C/HGV foi detectado em 13/73 (17,57 por cento) mulheres saudáveis e sua prevalência entre participantes da idade de 28-43 anos foi de 53,85 por cento. Não foi observada relação entre a presença do RNA GBV-C/HGV com a idade de primeira relação sexual, nem com o número de gestações. Entre as mulheres que apresentavam o RNA viral, 69,23 por cento eram casadas. O presente estudo demonstrou que secreções cérvico-vaginais podem conter o RNA viral GBV-C/HBV.