Month: March 2020

These factors complicate study of the gastrointestinal microbiota, and direct comparison of results between studies may be problematic. However, comparison of the composition of the microbiota between groups of animals within a study such as ours is not subject to as many of these limitations, and is likely to generate more meaningful results. Our results showed that the Torin 1 presence of insulin-treated diabetes mellitus in cats does not affect faecal microbiota composition, as evaluated by the UniFrac distance metric or by comparison of relative abundances of predominant bacterial taxa identified by sequencing of the 16S rRNA gene. We were therefore unable to replicate the results of Serino et al. who described a decreased proportion of Firmicutes in mice with type 2 diabetes mellitus, or Larsen et al. who reported a similar finding in type 2 diabetic men, in cats with diabetes mellitus. It is possible that the inability to identify a difference in microbiota composition between diabetic and non-diabetic cats could have been due to the relatively small sample size in this study; however, previous studies that have reported compositional differences of the microbiota associated with obesity, type 2 diabetes and type 1 diabetes have studied a similar number of or fewer individuals, making type II error unlikely. An additional consideration is that all diabetic cats in this study were treated with insulin, this being standard therapy for feline diabetes mellitus. Whether or not exogenous insulin can alter microbiota composition and/or obscure diabetesassociated changes in microbiota composition is unknown, however future studies could explore this issue by studying diabetic cats at the time of diagnosis, prior to commencement of insulin therapy. Compositional analysis of the microbiota, as undertaken in this study, may overlook the complexities of microbial communities in vivo. In a recent study, faecal microbiota of children was examined at several time points up to three years of age, and the microbiota composition of children who developed anti-islet cell antibodies was compared with children who remained antibody-free. No differences in microbiota composition, relative proportions of bacteria at genus level, or diversity were noted between groups. However when a microbial correlation network was constructed, a significant difference was noted in microbial interaction networks between the two groups of children. It was concluded that despite an absence of compositional differences, microbial interaction networks were compromised in children who developed anti-islet cell antibodies. This study demonstrates that disease-associated alterations of the faecal microbiota may not necessarily be discernible as quantitative compositional changes; and that consideration of intramicrobiota relationships may afford a more comprehensive assessment of the microbiota. Importantly, failure to identify compositional differences of faecal microbiota between diabetic and non-diabetic cats does not exclude the possibility of functional differences of the microbiota in affected individuals. Host metabolic effects may not be entirely predictable by a particular microbiota composition.

IL-8, a molecule shown to inhibit antitumor immune responses when it was peri/intra-tumoraly injected. Hyaluronic acid is a lineal, large and ubiquitous glycosaminoglycan with a simple chemical BAY-60-7550 structure found mainly in tissues undergoing cell proliferation, regeneration and repair. HA functions are well known to be size-dependent and the LMW HA form has been shown to induce the expression of proinflammatory genes such as IL-8, IL-12, TNF-a and inducible NO synthase in many types of cells including DC. In addition, LMW HA or its small fragments were shown to stimulate T cell responses by activating and up-regulating co-stimulatory molecules on DC in a CD44-independent and TLR4-dependent manner. Moreover, it has also been demonstrated that LMW HA can act as an adjuvant promoting antigen-specific T cell responses in vivo through TLR2 stimulation. The aim of this work was to evaluate the effects of LMW HA pre-conditioning on tumor-pulsed human DC obtained from both healthy donors and CRC patients. We found that LMW HA induced DC/TL maturation state able to enhance lymphocyte proliferation, and most importantly increasing their migratory capacity and avoiding tumor tissue attraction. These results provide the rationale for the potential use of LMW HA as an immunostimulatory molecule for DC-based vaccines protocols in the treatment of cancer patients. Our previous results showed that pre-incubation of DC with LMW HA was able to induce an efficient antitumoral effect in a CRC mouse model which was found to be mediated by the stimulation of DC maturation and activation, as well as by the induction of a potent migratory capacity towards lymphoid areas in vitro and in vivo. In the present study we demonstrated that LMW HA represents a potent stimulator of migration toward lymph node for human DC obtained from both HD and CRC patients, likely partially involving CCR7/CCL21 axis and inducing resistance to IL-8, a tumor-derived DC chemoattractant. In addition, LMW HA treatment enhanced MLR-stimulating capacity of DC in an in vivo assay. Thus, this work adds new data regarding the ability of LMW HA to improve migratory capacity of DC that could be relevant in future design of potential cancer vaccines protocols. Different studies showed that oligosaccharides of HA, but not high molecular weight HA, can be used to stimulate immune responses involving DC activation. Nevertheless, this is the first report addressing LMW HA effects on DC derived from patients with cancer and on their migratory response to lymph node signals. As expected, DC/TL from HD showed higher expression levels of maturation markers than those obtained from CRC patients. LMW HA was able to induce stimulatory effects on DC promoting an up-regulation of MHC-II and the co-stimulatory molecule CD86 when obtained from HD samples but not in those from CRC patients. This result could be, at least in part, due to the immunosuppressive state of cancer patients.

Being considered one of the most important sources of allergens for humans. Among asthmatic patients, sensitivity to dust mites is present in 50% of adults and 80% of children. The term “house dust mite” has been adopted to describe mite species that can be found in the indoor environment and have the ability to elicit a response resulting in IgE antibodies. Given the key role of cytokines in allergic reactions, gene variability in their regulatory regions might induce changes in the immune response. Regulatory regions have shown an influence on cytokine production and MK-4827 transcription. Cytokines participate not only in the regulation of the immune response, but also directly in the inflammatory response. The involvement of interleukins in the pathogenesis of a range of diseases, such as lupus erythematosus, diabetes, chronic periodontitis, and cancer, has been widely studied. However, little is known about the association between single nucleotide polymorphisms in cytokine genes and sensitivity to dust mites. Allergy is a multifactorial condition, with the onset and severity dependent on genetic and environmental factors. Hypersensitivity to house dust mites may trigger different cutaneous and respiratory responses, which have a great impact on the health of affected individuals. The discoveries made in the 1950s about the mechanisms of gene regulation in prokaryotes, such as lac or lambda repressor, have allowed researchers to investigate DNA binding sites in the regulatory regions of eukaryotes. Since then, several regulatory regions have been detected upstream and downstream of the transcribed gene, mainly in SNP regions. The development of molecular biology techniques has allowed the identification of genetic polymorphisms within regulatory regions of cytokine genes, and also the finding that the level of cytokine production differs among individuals. These considerations have prompted many authors to investigate the regulation of genes expressing these cytokines in relation to susceptibility to and severity of different diseases. Although cytokines are usually related to allergic diseases, such as allergic rhinitis, allergic conjunctivitis, food allergy, atopic dermatitis, and asthma, they have been suggested as important biomarkers of various diseases, such as lupus erythematosus, pediatric ulcerative colitis, Alzheimer’s disease, and ankylosing spondylitis. There is an increasing number of studies devoted to this topic in the international literature. However, to date, there are no studies conducted in Brazil that address this issue. A cohort study of asthma in the Korean population suggested a possible involvement of IL18 polymorphisms in asthma. Moreover, cytokines play an important physiological role in immune regulation and inflammatory processes, and changes in the aberrant expression or failure in production may contribute to the development of certain diseases.

Therefore, misreported data could have biased our findings. Fifth, we did not examine the consumption of animal protein, which is regarded as high-protein diet and associated with increased intake of purines. The different habits of animal protein consumption between women and men may have affected our results. Sixth, we did not examine the glucocorticoids during the awaking process, which has a considerable influence on fasting glucose. The rise of glucocorticoids increases glycogen hydrolysis in the liver, increasing its LY2157299 side effects glucose output and eliciting temporal hyperglycemia, which may be confused by diabetes. Finally, we investigated a solely Japanese population, which could limit the generalizability of our results to other populations. To correct these limitations, future studies should use a prospective validation design, and investigate diverse populations that present at various outpatient medical practices. Despite these limitations, our study produced several noteworthy results. In particular, our findings suggest that hyperuricemia is a risk factor for the onset of impaired fasting glucose among persons with high baseline fasting plasma glucose. To help prevent the onset of impaired fasting glucose and the development of further complications, we should therefore pay careful attention to both uric acid levels and fasting plasma glucose levels, especially in subjects with hyperuricemia. It might be possible to prevent impaired fasting glucose and the development of further complications by treating both elevated fasting plasma glucose and hyperuricemia, although randomized studies would be necessary to validate this suggestion. The prevalence of allergic diseases has experienced an important increase in industrialized countries over recent decades. Although this increase has been widely investigated, the reasons for such trend have not yet been elucidated. According to the World Allergy Organization, children carry the greatest burden of the rising trend which has occurred over the past two decades. Despite this increase, in many countries there are no specialized services for patients with allergic diseases. In respiratory allergies, such as asthma and rhinitis, there is inflammation of the airways as a result of an immune reaction, with release of cytoplasmic granules from active substances found in mast cells, basophils, and eosinophils. Two main factors contribute to the development and severity of allergic disease: host-related factors and environmental factors, such as specific allergens, elements present in the environment, and air pollutants. When combined, these factors may trigger sensitization. In addition, there is the “hygiene hypothesis”, which became popular in the late 1980s to explain the high prevalence of atopic diseases in developed countries. It supports the idea that a reduced exposure to infections during childhood would predispose individuals to sensitization.

It is possible to find multiple RNA polymerase pausing sites along a gene sequence. Remarkably, it was clear from gene expression profiles that dynamical behavior of a TSSaRNA may be distinct from that of its cognate gene. In some cases, the cognate gene level does not change, but expression of the TSSaRNA has distinct dynamics, with up to 16 fold up-regulation or down-regulation to different degrees. We also observed instances when both TSSaRNA and cognate gene were differentially regulated, albeit with different patterns. Imposing stringent criteria, we identified at least 10 TSSaRNA differentially expressed relative to their cognate genes. Such differential expression patterns would not be expected if transcription of a TSSaRNA and the full-length transcript of its cognate gene were not regulated by environmental signals, nor could it arise as an experimental artifact of tiling array hybridization and processing. Using pausing sites that can vary their retention time along the growth curve, the RNA polymerase pausing model explains our experimental observation that TSSaRNA can have distinct dynamical behavior relative to their cognate gene. LY2109761 700874-71-1 Although counterintuitive, it is possible to generate dynamical profiles such as the ones where TSSaRNA levels remains constant and its cognate gene varies and vice versa, only exploring the two parameters of the model: elapsed time spent paused and time between successive transcripts initiation events. Therefore, our transcriptome analysis indicates that there is probably RNA polymerase pausing rhythm regulation in response to environmental perturbations. Future experimental work would reveal how this rhythm may be tuned and what are the implication of this regulation. In this study we analyzed the transcriptome of 11 archaea: Halobacterium salinarum NRC-1, Pyrococcus furiosus DSM 3638, Methanococcus maripaludis S2, Sulfolobus solfataricus P2, Nanoarchaeum equitans Kin4-M, Methanopyrus kandleri AV19, Sulfolobus acidocaldarius MW001, Haloferax volcanii DS2, Methanolobus psycrophilus R15, Methanosarcina mazei Go¨1 and Pyrococcus abyssi. Only S. acidocaldarius data did not present sufficient coverage to clearly show at least one TSSaRNAs signature. Therefore, our observations were made for 10 organisms. Archaeal transcriptomes for which dynamical information was available were highlighted in this work: Halobacterium salinarum NRC-1, Pyrococcus furiosus DSM 3638, Methanococcus maripaludis S2 and Sulfolobus solfataricus P2. Original accession numbers for these datasets are: GSE13150, GSE18630, GSE38821, GSE26782, GSE44979, SRP028191, SRX188664. Datasets not available in public databases were obtained directly from publications. A brief description for each dataset used is provided in the Table S3. The expression signal for putative TSSaRNAs locations is a distinct signature characterized by a sharp rise in signal that plateaus over a relatively small distance and then decays precipitously.