21 research outputs found
Принципи управління персоналом сільськогосподарських підприємств (на прикладі Луганської області)
У статті проаналізовано сучасний стан сільськогосподарського виробництва в Луганській
області та здійснена оцінка перспектив реформування управління персоналом на підприємствах АПК. Регресійним аналізом оцінено ступінь впливу деяких факторів на рентабельність персоналу. Рекомендується використання SWOT-аналізу для дослідження й формування раціонального управління персоналом підприємств АПК.Performed analysis of the current state of agriculture in the Luhansk region, evaluated the prospects for personnel
resources reforming for the agricultural enterprises. The degree of factors influencing on profitability of personnel is
appraised by the regressive analysis. SWOT-analysis is recommended for research and forming of agrarian enterprises
rational management of a personnel
Canonical Wnt signaling negatively modulates regulatory T cell function
Foxp3 is crucial for both the development and function of regulatory T (Treg) cells; however, the posttranslational mechanisms regulating Foxp3 transcriptional output remain poorly defined. Here, we demonstrate that Tcell factor 1 (TCF1) and Foxp3 associates in Treg cells and that active Wnt signaling disrupts Foxp3 transcriptional activity. A global chromatin immunoprecipitation sequencing comparison in Treg cells revealed considerable overlap between Foxp3 and Wnt target genes. The activation of Wnt signaling reduced Treg-mediated suppression both invitro and invivo, whereas disruption of Wnt signaling in Treg cells enhanced their suppressive capacity. The activation of effector Tcells increased Wnt3a production, and Wnt3a levels were found to be greatly increased in mononuclear cells isolated from synovial fluid versus peripheral blood of arthritis patients. We propose a model in which Wnt produced under inflammatory conditions represses Treg cell function, allowing a productive immune response, but, if uncontrolled, could lead to the development of autoimmunity
Redefining Strategies to Introduce Tolerance-Inducing Cellular Therapy in Human beings to Combat Autoimmunity and Transplantation Reactions
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Different cytokine signatures in children with localized and invasive adenovirus infection after stem cell transplantation
P>HAdV infection is a dangerous complication after pediatric SCT. In this study, we aimed at determining the cytokine profile in plasma samples in case of HAdV infection after SCT to gain more knowledge about the HAdV-specific immune response. In this prospective study, 47 pediatric SCT recipients were included in three yr. By using particle-based MIA, 17 different cytokines were analyzed in 41 plasma samples of patients with a localized HAdV infection (presence of HAdV in feces, urine or throat detected by culture) and patients with invasive HAdV infection (HAdV viremia in blood, detected by PCR). In patients with invasive HAdV infection, but not in patients with localized HAdV infection, the pro-inflammatory cytokines IL1 beta, IL6, IL8, IL12, IFN gamma, TNF alpha, and also IL17, MIP1 alpha, OSM, and IP10 were produced. The simultaneous release of the cytokines IL1 beta, IL17, IL18, OSM, MIP1 alpha, and IP10 was related to invasive HAdV infections. We also show that cytokine signatures can be helpful to differentiate invasive HAdV infection from GvHD and EBV infections. In conclusion, after SCT, children with invasive HAdV infection have a different cytokine profile compared with patients with a localized HAdV infection.Molecular basis of virus replication, viral pathogenesis and antiviral strategie
Effectiveness of first line use of recombinant IL-1RA treatment in steroid naïve systemic juvenile idiopathic arthritis: Results of a prospective cohort study
Treatment-specific changes in circulating adipocytokines: a comparison between tumour necrosis factor blockade and glucocorticoid treatment for rheumatoid arthritis
Objective There is increasing evidence that adipocytokines may exert proinflammatory and destructive effects in rheumatoid arthritis (RA). Hence, the authors investigated the relationship between adipocytokines and several features associated with RA (inflammation, joint destruction and cardiovascular disease), as well as the effect of treatment with a tumour necrosis factor inhibitor or glucocorticoids (GCs) hereupon. Methods Serum levels of adiponectin, leptin, resistin, visfatin, vaspin and lipids were determined in a well-defined cohort of patients with RA before and after 16 weeks of adalimumab treatment (adalimumab cohort). The same parameters were analysed in two other cohorts of patients with RA before and after 2 weeks of high-dose prednisolone (high GC cohort) and before and after 22 weeks of treatment with a combination regimen with tapered high-dose prednisolone (COBRA-GC cohort). Radiographs of hands and feet (adalimumab and COBRA-GC cohorts) were assessed at baseline and after treatment. Results Treatment with adalimumab or GC showed opposing effects on vaspin and visfatin levels. Lipid levels improved after several months of adalimumab or GC treatment; in the adalimumab cohort, this was related to reduced visfatin levels, independent of C reactive protein levels. After long-term adalimumab or GC treatment, resistin levels declined, which was associated with a decrease in inflammation markers. In the adalimumab cohort, baseline resistin levels were predictive of baseline radiological damage, independent of anticitrullinated peptide antibodies status or C reactive protein levels. Conclusion Changes in serum adipocytokine levels were treatment specific, further strengthening the role of visfatin and resistin in several disease manifestations of R
Lactic acid bacteria differ in their ability to induce functional regulatory T cells in humans.
Item does not contain fulltextBACKGROUND: Trials with probiotic lactic acid bacteria have yielded different results, which may be due to the strains used. Lactobacilli and bifidobacteria are known to be potent modulators of the immune system. The capacity of these bacteria used as probiotics to influence both T helper type 1 (Th1)- and Th2-mediated diseases has been shown before. However, the ability of strains to induce forkhead box P3 (FOXP3(+)) expressing regulatory T cells has not yet been investigated. OBJECTIVE: Test the inherent differences between strains in their capacity to induce functional regulatory T cells in human peripheral blood mononuclear cells (PBMC). METHODS: Human PBMC were co-cultured in vitro with either Bifidobacterium lactis W51, Lactobacillus acidophilus W55 or Lactobacillus plantarum W62 or an Escherichia coli control strain. The percentage of FOXP3(+) cells, the origin of the induced cells and the functionality of these cells were assessed. Results Probiotic strains differ in their capacity to induce regulatory T cells. FOXP3(+) cells were induced from CD25(-) cells and were able to suppress effector T cells. Naturally occurring regulatory T cells were not affected by co-culture with lactobacilli. IL-10 concentrations found in the supernatant showed a trend towards the same differences between strains. Blockade of IL-10 did not influence the up-regulation of FOXP3. No differences between lactic acid bacteria were found in IL-17, IFN-gamma or IL-13. CONCLUSIONS: Some probiotic strains are potent inducers of regulatory cells, while others are not. The clear differences between strains imply that an in vitro characterization of probiotic strains before application is recommended.1 januari 201
Increased immune reactivity towards human hsp60 in patients with primary Sjogren's syndrome is associated with increased cytokine levels and glandular inflammation
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Cartilage proteoglycan aggrecan epitopes induce proinflammatory autoreactive T-cell responses in rheumatoid arthritis and osteoarthritis.
Item does not contain fulltextOBJECTIVES: To explore potential T-cell epitopes of the core protein of human cartilage proteoglycan aggrecan (PG) in patients with rheumatoid arthritis (RA) or osteoarthritis. METHODS: Peptide-specific T-cell proliferation and cytokine/chemokine production in response to PG-specific peptides were measured in RA and osteoarthritis patients and in healthy controls. RESULTS: Peptides representing amino acid regions 16-39 and 263-282 of PG were most frequently recognised by T cells in a subset of patients with RA or osteoarthritis. Peripheral blood mononuclear cells from these PG-reactive RA and osteoarthritis patients showed increased production of proinflammatory cytokines/chemokines in response to PG peptide stimulation. As PG p263-282 was found to show high sequence homology with Yersinia Yop protein, the corresponding bacterial (Yersinia) peptide was also tested. Remarkably, RA and osteoarthritis patients responding to the Yersinia peptide also responded to p263-282 of PG suggesting a possibility of molecular mimicry in these patients. CONCLUSIONS: These results indicate that PG-specific peptides, located in the G1 domain of PG, can induce (auto)antigenic T-cell responses in RA and osteoarthritis patients. These peptides might thus be involved in the immune pathogenesis and/or cartilage degradation in RA and osteoarthritis.1 januari 201
Regulation of Treg functionality by acetylation-mediated Foxp3 protein stabilization.
Regulatory T cells (Tregs) are a specific
subset of lymphocytes that are critical for
the maintenance of self-tolerance. Expression
levels of the transcription factor
Foxp3 have been causally associated with
Treg differentiation and function. Recent
studies show that Foxp3 can also be
transiently expressed in effector T cells;
however, stable Foxp3 expression is required
for development of a functional
Treg suppressor phenotype. Here, we
demonstrate that Foxp3 is acetylated, and
this can be reciprocally regulated by the
histone acetyltransferase p300 and the
histone deacetylase SIRT1. Hyperacetylation
of Foxp3 prevented polyubiquitination
and proteasomal degradation, therefore
dramatically increasing stable Foxp3
protein levels. Moreover, using mouse
splenocytes, human peripheral blood
mononuclear cells, T cell clones, and
skin-derived T cells, we demonstrate that
treatment with histone deacetylase inhibitors
resulted in significantly increased
numbers of functional Treg cells. Taken
together, our data demonstrate that modulation
of the acetylation state of Foxp3
provides a novel molecular mechanism
for assuring rapid temporal control of
Foxp3 levels in T cells, thereby regulating
Treg numbers and functionality. Manipulating
Foxp3 acetylation levels could
therefore provide a new therapeutic strategy
to control inappropriate (auto)immune
responses