Роль русского языка и литературы в формировании межкультурной компетенции иностранных студентов-филологов

Contains fulltext : 176878.pdf (publisher's version ) (Open Access)Orally ingested bacteria interact with intestinal mucosa and may impact immunity. However, insights in mechanisms involved are limited. In this randomized placebo-controlled cross-over trial, healthy human subjects were given Lactobacillus plantarum supplementation (strain TIFN101, CIP104448, or WCFS1) or placebo for 7 days. To determine whether L. plantarum can enhance immune response, we compared the effects of three stains on systemic and gut mucosal immunity, by among others assessing memory responses against tetanus toxoid (TT)-antigen, and mucosal gene transcription, in human volunteers during induction of mild immune stressor in the intestine, by giving a commonly used enteropathic drug, indomethacin [non-steroidal anti-inflammatory drug (NSAID)]. Systemic effects of the interventions were studies in peripheral blood samples. NSAID was found to induce a reduction in serum CD4+/Foxp3 regulatory cells, which was prevented by L. plantarum TIFN101. T-cell polarization experiments showed L. plantarum TIFN101 to enhance responses against TT-antigen, which indicates stimulation of memory responses by this strain. Cell extracts of the specific L. plantarum strains provoked responses after WCFS1 and TIFN101 consumption, indicating stimulation of immune responses against the specific bacteria. Mucosal immunomodulatory effects were studied in duodenal biopsies. In small intestinal mucosa, TIFN101 upregulated genes associated with maintenance of T- and B-cell function and antigen presentation. Furthermore, L. plantarum TIFN101 and WCFS1 downregulated immunological pathways involved in antigen presentation and shared downregulation of snoRNAs, which may suggest cellular destabilization, but may also be an indicator of tissue repair. Full sequencing of the L. plantarum strains revealed possible gene clusters that might be responsible for the differential biological effects of the bacteria on host immunity. In conclusion, the impact of oral consumption L. plantarum on host immunity is strain dependent and involves responses against bacterial cell components. Some strains may enhance specific responses against pathogens by enhancing antigen presentation and leukocyte maintenance in mucosa. In future studies and clinical settings, caution should be taken in selecting beneficial bacteria as closely related strains can have different effects. Our data show that specific bacterial strains can prevent immune stress induced by commonly consumed painkillers such as NSAID and can have enhancing beneficial effects on immunity of consumers by stimulating antigen presentation and memory responses

Anti-inflammatory nutrition with high protein attenuates cardiac and skeletal muscle alterations in a pulmonary arterial hypertension model

Pulmonary arterial hypertension (PAH) is characterized by remodelling of the pulmonary arteries and right ventricle (RV), which leads to functional decline of cardiac and skeletal muscle. This study investigated the effects of a multi-targeted nutritional intervention with extra protein, leucine, fish oil and oligosaccharides on cardiac and skeletal muscle in PAH. PAH was induced in female C57BL/6 mice by weekly injections of monocrotaline (MCT) for 8 weeks. Control diet (sham and MCT group) and isocaloric nutritional intervention (MCT + NI) were administered. Compared to sham, MCT mice increased heart weight by 7%, RV thickness by 13% and fibrosis by 60% (all p < 0.05) and these were attenuated in MCT + NI mice. Microarray and qRT-PCR analysis of RV confirmed effects on fibrotic pathways. Skeletal muscle fiber atrophy was induced (P < 0.05) by 22% in MCT compared to sham mice, but prevented in MCT + NI group. Our findings show that a multi-targeted nutritional intervention attenuated detrimental alterations to both cardiac and skeletal muscle in a mouse model of PAH, which provides directions for future therapeutic strategies targeting functional decline of both tissues

The discovery of Hepatocyte Growth Factor (HGF) and its significance for cell biology, life sciences and clinical medicine

It has been more than 25 years since HGF was discovered as a mitogen of hepatocytes. HGF is produced by stromal cells, and stimulates epithelial cell proliferation, motility, morphogenesis and angiogenesis in various organs via tyrosine phosphorylation of its receptor, c-Met. In fetal stages, HGF-neutralization, or c-Met gene destruction, leads to hypoplasia of many organs, indicating that HGF signals are essential for organ development. Endogenous HGF is required for self-repair of injured livers, kidneys, lungs and so on. In addition, HGF exerts protective effects on epithelial and non-epithelial organs (including the heart and brain) via anti-apoptotic and anti-inflammatory signals. During organ diseases, plasma HGF levels significantly increased, while anti-HGF antibody infusion accelerated tissue destruction in rodents. Thus, endogenous HGF is required for minimization of diseases, while insufficient production of HGF leads to organ failure. This is the reason why HGF supplementation produces therapeutic outcomes under pathological conditions. Moreover, emerging studies delineated key roles of HGF during tumor metastasis, while HGF-antagonism leads to anti-tumor outcomes. Taken together, HGF-based molecules, including HGF-variants, HGF-fragments and c-Met-binders are available as regenerative or anti-tumor drugs. Molecular analysis of the HGF-c-Met system could provide bridges between basic biology and clinical medicine

Elucidating the mechanism behind the lipid-raising effect of cafestol

The objective of this thesis was to identify genes that control the response of serum lipid levels to diet. To this end we used cafestol as model substance for a food component that affects serum lipids and therefore health. Cafestol is a cholesterol‑raising diterpene present in coffee beans and unfiltered coffee types.A possible explanation for the cholesterol-raising effect of cafestol is inhibition of bile acid synthesis. This is observed in APOE3Leiden mice upon treatment with cafestol. The nuclear receptors FXR and PXR are key regulators of genes involved in lipid and bile acid metabolism and detoxification.Both these nuclear receptorscan mediate inhibition of cholesterol 7a‑hydroxylase, the rate-limiting enzyme in bile acid synthesis. Therefore, we hypothesized that cafestol is able to activate FXR and/or PXR.We used promoter-reporter gene assays to show that cafestol interacts with FXR and PXR in vitro .This suggests that cafestol can regulate gene expression via these receptors. Indeed cafestol regulated several mRNA levels of target genes of FXR and PXR in livers of APOE3Leiden mice. For a number of target genes these effects were absent in livers of FXR and PXR knockout mice. This confirms that FXR and PXR are involved in the regulation of gene expression by cafestol. However, we could not confirm suppression of bile acid synthesis in humans. We measured plasma levels of7a‑hydroxy-4-cholesten-3-one, a marker for activity of cholesterol 7a‑hydroxylase, in volunteers that consumed coffee oil. Surprisingly, we observed an increase rather than a decrease in the level of 7a‑hydroxy‑4‑cholesten‑3‑one upon coffee oil treatment. In conclusion, it is likely that the interaction with FXR and PXR is at least partly responsible for the effect of cafestol on serum lipids in humans. However, the exact mechanism by which cafestol raises serum cholesterol remains to be elucidated. Elucidation of this mechanism will provide insight into how dietary components can affect serum lipid levels

Evaluation of functional properties of current and novel protein sources using enteroids

This study was designed to address key questions concerning the use of alternative protein sources for animal feeds and addresses aspects such as their nutrient composition and impact on gut function. We used casein (CAS), spray dried porcine plasma (SDPP), soybean meal (SBM), and yellow meal worm (YMW) as protein sources. We have investigated the use of intestinal organoids as a model to test the effects of different protein sources on the intestinal epithelium. Mouse enteroids were exposed to different undigested protein sources (4% w/v, viz. soybean meal, SBM; casein, CAS; spray dried plasma protein, SDPP; and yellow meal worm, YMW) or DMEM as a control. Microarrays were used to detail the global gene expression

Evaluation of functional properties of current and novel protein sources using enteroids

This study was designed to address key questions concerning the use of alternative protein sources for animal feeds and addresses aspects such as their nutrient composition and impact on gut function. We used casein (CAS), spray dried porcine plasma (SDPP), soybean meal (SBM), and yellow meal worm (YMW) as protein sources. We have investigated the use of intestinal organoids as a model to test the effects of different protein sources on the intestinal epithelium. Mouse enteroids were exposed to different undigested protein sources (4% w/v, viz. soybean meal, SBM; casein, CAS; spray dried plasma protein, SDPP; and yellow meal worm, YMW) or DMEM as a control. Microarrays were used to detail the global gene expression

A Robust Auxin Response Network Controls Embryo and Suspensor Development through a bHLH Transcriptional Module

Land plants can reproduce sexually by developing an embryo from a fertilized egg cell. However, embryos can also be formed from other cell types in many plant species. A key question is thus how embryo identity in plants is controlled, and how this process is modified during non-zygotic embryogenesis. The Arabidopsis zygote divides to produce an embryonic lineage and an extra-embryonic suspensor. Yet, normally quiescent suspensor cells can develop a second embryo when the initial embryo is damaged, or when response to the signaling molecule auxin is locally blocked. Here we have used auxin-dependent suspensor embryogenesis as a model to determine transcriptome changes during embryonic reprogramming. We find that reprogramming is complex and accompanied by large transcriptomic changes prior to anatomic changes. This analysis revealed a strong enrichment for genes encoding components of auxin homeostasis and response among misregulated genes. Strikingly, deregulation among multiple auxin-related gene families converged upon re-establishment of cellular auxin levels or response. This suggests a remarkable degree of feedback regulation to create resilience in auxin response during embryo development. Starting from the transcriptome of auxin-deregulated embryos, we identify an auxin-dependent bHLH transcription factor network that mediates the activity of this hormone in suppressing embryo development from the suspensor

The effect of probiotic Lactobacilli strains, inulin-type fructans and oligofructose on gene expression profiles in intestinal Caco-2 cells

Background: Beneficial microbes can be actors in maintaining or stimulating barrier function, and may counteract pathogen-infection. Lactobacilli are particularly recognized for enhancing intestinal barrier function and to confer protective effects against multiresistant pathogens. Various L. acidophilus strains support intestinal immune barrier function and have been shown to improve resistance to pathogens. Although less extensively studied than beneficial bacteria, other food-based ingredients that can contribute to strengthening barrier function are dietary fibers. For instance, inulin and fructooligosaccharides (FOS) have recently been shown to enhance barrier function and protect against barrier dysfunction. Effects of these ingredients on intestinal barrier function were evaluated by quantifying regulation of gene expression by microarray. Methods: Caco-2 cells were incubated with probiotic strains or inulin-type fibers for 6 hours, total RNA was extracted and Affymterix Human Gene 1.1 ST arrays were used to analyze the gene expression profiles. Results: Only L. acidophilus modulated a group of 26 genes related to tight-junctions. Inulin-type fructans, L. brevis W63 and L. casei W56 regulated other genes, unrelated to tight junctions. L. acidophilus also had unique effects on a group of 6 genes regulating epithelial phenotype towards follicle-associated epithelium. L. acidophilus W37 was therefore selected for a challenge with STM and prevented STM-induced barrier disruption and decreased secretion of IL-8. L. acidophilus W37 increases TEER and can protect against STM induced disruption of gut epithelial cells integrity in vitro. Conclusion: Our results suggest that selection of specific bacterial strains for enforcing barrier function may be a promising strategy to reduce or prevent STM infections