Gut microbiome signature and nasal lavage inflammatory markers in young people with asthma.

Background: Asthma is a complex disease and a severe global public health problem resulting from interactions between genetic background and environmental exposures. It has been suggested that gut microbiota may be related to asthma development; however, such relationships needs further investigation. Objective: This study aimed to characterize the gut microbiota as well as the nasal lavage cytokine profile of asthmatic and nonasthmatic individuals. Methods: Stool and nasal lavage samples were collected from 29 children and adolescents with type 2 asthma and 28 children without asthma in Brazil. Amplicon sequencing of the stool bacterial V4 region of the 16S rRNA gene was performed using Illumina MiSeq. Microbiota analysis was performed by QIIME 2 and PICRUSt2. Type 2 asthma phenotype was characterized by high sputum eosinophil counts and positive skin prick tests for house dust mite, cockroach, and/or cat or dog dander. The nasal immune marker profile was assessed using a customized multiplex panel. Results: Stool microbiota differed significantly between asthmatic and nonasthmatic participants (P = .001). Bacteroides was more abundant in participants with asthma (P < .05), while Prevotella was more abundant in nonasthmatic individuals (P < .05). In people with asthma, the relative abundance of Bacteroides correlated with IL-4 concentration in nasal lavage samples. Inference of microbiota functional capacity identified differential fatty acid biosynthesis in asthmatic compared to nonasthmatic subjects. Conclusion: The stool microbiota differed between asthmatic and nonasthmatic young people in Brazil. Asthma was associated with higher Bacteroides levels, which correlated with nasal IL-4 concentration.

Apoptosis Transcriptional Profile Induced by Porphyromonas gingivalis HmuY.

This study aimed at evaluating the transcriptional profile of apoptosis-related genes after in vitro stimulation of peripheral blood mononuclear cells (PBMCs) derived from individuals with periodontitis (P) and healthy nonperiodontitis (NP) control subjects with P. gingivalis HmuY protein. PBMCs from the P and NP groups were stimulated with HmuY P. gingivalis protein, and the expression of genes related to apoptosis was assessed by custom real-time polymerase chain reaction array (Custom RT2 PCR Array). Compared with the NP group, the P group showed low relative levels of apoptosis-related gene expression, downregulated for FAS, FAS ligand, TNFSF10 (TRAIL), BAK1, CASP9, and APAF1 after P. gingivalis HmuY protein stimulation. Furthermore, the P group exhibited low levels of relative gene expression, downregulated for CASP7 when the cells were not stimulated. Our data suggest that P. gingivalis HmuY protein might participate differently in the modulation of the intrinsic and extrinsic apoptosis pathways.

Endoglin: a novel target for therapeutic intervention in acute leukemias revealed in xenograft mouse models.

Endoglin (CD105), a receptor of the transforming growth factor-ß superfamily, has been reported to identify functional long-term repopulating hematopoietic stem cells, and has been detected in certain subtypes of acute leukemias. Whether this receptor plays a functional role in leukemogenesis remains unknown. We identified endoglin expression on the majority of blasts from patients with acute myeloid leukemia (AML) and acute B-lymphoblastic leukemia (B-ALL). Using a xenograft model, we find that CD105+ blasts are endowed with superior leukemogenic activity compared with the CD105- population. We test the effect of targeting this receptor using the monoclonal antibody TRC105, and find that in AML, TRC105 prevented the engraftment of primary AML blasts and inhibited leukemia progression following disease establishment, but in B-ALL, TRC105 alone was ineffective due to the shedding of soluble CD105. However, in both B-ALL and AML, TRC105 synergized with reduced intensity myeloablation to inhibit leukemogenesis, indicating that TRC105 may represent a novel therapeutic option for B-ALL and AML.

Produtos naturais utilizados para tratamento de asma em crianças residentes na cidade de Salvador-BA, Brasil / Natural products used for asthma treatment in children living in Salvador-BA, Brazil

O conhecimento popular é o passo inicial para a investigação científica de atividades terapêuticas de remédios caseiros. Diversas patologias podem ser tratadas ou amenizadas através de preparações de origem natural e muitos fármacos disponíveis são oriundos de fontes naturais. Este trabalho tem como objetivo avaliar o uso de remédios caseiros derivados de plantas para tratamento de asma em crianças residentes no município de Salvador. Os dados foram obtidos a partir de estudo realizado em Salvador sobre fatores de risco, uso de medicações e vias imunológicas relacionadas à asma em crianças. Foram calculadas as freqüências de uso de preparações caseiras para tratamento de asma por esta população e realizado uma revisão bibliográfica sobre os efeitos das plantas mais usadas. Dentre as espécies mais citadas, destacam-se o Allium sativum (alho) que teve a maior freqüência de utilização na preparação dos remédios caseiros (25 por cento), seguido da Allium cepa (cebola, 19,74 por cento). Após a revisão crítica de literatura, constatou-se que a maioria das espécies é utilizada com base em relatos fundamentados no saber popular, sendo assim carente de evidências científicas para as atividades farmacoterapêuticas esperadas. Neste sentido, há necessidade de mais estudos farmacológicos para comprovação das atividades terapêuticas peculiares a cada produto de origem natural bem como para avaliar possíveis efeitos tóxicos destes produtos.

The popular knowledge is the initial step for the scientific inquiry of therapeutical activities of herb-based remedies. Several pathologies can be treated or brightened up through this kind of preparations and also many of the available drugs in the market have natural sources. The objective of this work was to evaluate the use of herb-based remedies for treatment of asthma in children in the city of Salvador. Data were collected by a standard questionnaire during a transversal study carried out in Salvador on risk factors, use of medications and immunological pathways involved in asthma. Among the most frequently mentioned species, the Allium sativum had the highest frequency of use in the preparation of home remedies (25 percent), followed by the Allium cepa (19.74 percent). The literature review showed that the majority of the species is empirically used based on popular knowledge and lacks on scientific evidences that prove their pharmacotherapeutic activities and safety for human use. In this way, this work not only new species unexplored in the context of anti-asthmatic drugs but it also highlights the need for new pharmacological studies in order to identify and prove the popular use of herb-based remedies.

An improved method to obtain antigen-excreting Toxocara canis larvae.

Toxocara canis is a dog helminth which causes visceral larva migrans (VLM) when infecting humans as a larva. The infection is demonstrated by detecting IgG antibodies against excretory-secretory larval antigens (ESLA) in serum by ELISA. The production of ESLA involves the collection of adult worms from dog puppy stools, the separation of eggs from dissected uteri, and the in vitro growing of egg-derived larvae, following the time-consuming and laborious protocol described by De Savigny [De Savigny, D.H., 1975. In vitro maintenance of T. canis larvae and a simple method for the production of Toxocara ES antigen for the uses in serodiagnostic tests for visceral larva migrans. Journal of Parasitology 61, 781-782]. In this work, an improved protocol for obtaining T. canis larvae is described. The modifications proposed improved the efficiency of the original De Savigny method in three ways: (i) increasing the parasite yield up to five fold, (ii) improving the larval purity, and (iii) markedly reducing the execution time of the protocol.

Effects produced by Royal Jelly on haematopoiesis: relation with host resistance against Ehrlich ascites tumour challenge.

Royal jelly (RJ) was shown to exhibit immunomodulatory properties, although its biological activity is still unclear. In order to elucidate the mechanism whereby RJ activates the immunological system, we examined the role of this substance on the haematopoietic response of Ehrlich ascites tumour (EAT)-bearing mice. Our results demonstrated that RJ prevented the myelosupression induced by the temporal evolution of the tumour and abrogated the splenic haematopoiesis observed in EAT-bearing mice. The stimulating effect of RJ was also observed in vitro on the multipotent bone marrow stem cells, evaluated by the long-term bone marrow cultures (LTBMCs). The study of survival clearly showed the antitumour activity of RJ. Treatment was given prophylactically for 20 days and therapeutically for 3, 8 and 13 days. Except for the treatment with the lower dose of 500 mg/kg, given for 23 days, all the other dose schedules were able to prolong survival. A more effective antitumoural response was observed with the more prolonged treatment regimen. In this regard, the administration of RJ for 33 days produced the highest protection reaching an extension of survival at about 38%, 71% and 85% for the doses of 500, 1000 and 1500 mg/kg, respectively, whereas with the 23 and 28 days treatment schedules, survival increased at a rate of 19% and 23%, respectively, and comparable results were found among the effective doses of RJ. Increased survival rate might be related to the decreased Prostaglandin E2 (PGE2) levels observed in EAT-bearing mice after RJ treatment. These results point to RJ as a promising modifier of biological response leading to myeloprotection and antitumour activity.

Protective effects of Chlorella vulgaris in lead-exposed mice infected with Listeria monocytogenes.

Chlorella vulgaris extract (CVE) was examined for its chelating effects on the myelosuppression induced by lead in Listeria monocytogenes-infected mice. The reduction in the number of bone marrow granulocyte-macrophage progenitors (CFU-GM) observed after the infection was more severe in the groups previously exposed to lead. Extramedullar hematopoiesis, which was drastically increased after the infection, was not altered by the presence of lead. Treatment with CVE, given simultaneously or following lead exposure, restored to control values the myelosuppression observed in infected/lead-exposed mice and produced a significant increase in serum colony-stimulating activity. The benefits of the CVE treatment were also evident in the recovery of thymus weight, since the reduction produced by the infection was further potentiated by lead exposure. The efficacy of CVE was evident when infected and infected/lead-exposed mice were challenged with a lethal dose of L. monocytogenes after a 10-day treatment with 50 mg/kg CVE/day, given simultaneously to the exposure to 1300 ppm lead acetate in drinking water. Survival rates of 30% for the infected group and of 20% for the infected/lead-exposed groups were observed. Evidence that these protective effects of CVE are partly due to its chelating effect was given by the changes observed in blood lead levels. We have observed in the group receiving the CVE/lead simultaneous exposure a dramatic reduction of 66.03% in blood lead levels, when compared to lead-exposed nontreated control. On the other hand, CVE treatment following lead exposure produced a much less effective chelating effect. CVE treatments for 3 or 10 days, starting 24 h following lead exposure, produced a reduction in blood lead levels of 13.5% and 17%, respectively, compared to lead-exposed nontreated controls. The significantly better response observed with the simultaneous CVE/lead administration indicates that the immunomodulation effect of CVE plays an important role in the ability of this algae to reduce blood lead levels. In this regard, additional experiments with gene knockout C57BL/6 mice lacking a functional IFN-gamma gene demonstrated that this cytokine is of paramount importance in the protection afforded by CVE. The antibacterial evaluation measured by the rate of survival demonstrated that, in face of a 100% survival in the control group composed of normal C57BL/6 mice, which are resistant to L. monocytogenes, we observed no protection whatsoever in the IFN-gamma knockout C57BL/6 mice treated with CVE and inoculated with L. monocytogenes.