Inflammation is a double-edged sword with both detrimental and beneficial consequences. Understanding of the mechanisms of crosstalk between the inflammatory milieu and human adult mesenchymal stem cells is an important basis for clinical efforts. Here, we investigate changes in the transcriptional response of human adipose-derived stem cells to physiologically relevant levels of IL-2 (IL-2 priming) upon replicative senescence. Our data suggest that replicative senescence might dramatically impede human mesenchymal stem cell (MSC) function via global transcriptional deregulation in response to IL-2. We uncovered a novel senescence-associated transcriptional signature in human adipose-derived MSCs hADSCs after exposure to pro-inflammatory environment: significant enhancement of the expression of the genes encoding potent growth factors and cytokines with anti-inflammatory and migration-promoting properties, as well as genes encoding angiogenic and anti-apoptotic promoting factors, all of which could participate in the establishment of a unique microenvironment. We observed transcriptional up-regulation of critical components of the nitric oxide synthase pathway (iNOS) in hADSCs upon replicative senescence suggesting, that senescent stem cells can acquire metastasis-promoting properties via stem cell-mediated immunosuppression. Our study highlights the importance of age as a factor when designing cell-based or pharmacological therapies for older patients and predicts measurable biomarkers characteristic of an environment that is conducive to cancer cells invasiveness and metastasis.
Background Over 60 years ago clinical patterns resembling tick-borne rickettsioses have been described for the first time in Kazakhstan. Since 1995 the incidence of clinical cases of tick-borne rickettsioses in humans seems to be rising but studies on epidemiological data regarding the occurring etiological agents, tick vector species, prevalence and distribution throughout Kazakhstan are still scarce to date. The aim of the study was molecular investigation of ticks for spotted-fever group rickettsiae in the endemic Kyzylorda region and the so far considered as non-endemic Almaty region. A total of 2341 ticks was collected in the two regions in Kazakhstan and sorted in 501 pools: Ixodes persulcatu s (243); Dermacentor marginatus (129); Haemaphysalis punctata (104); Hyalomma asiaticum (17); Dermacentor reticulatus (3); and Rhipicephalus turanicus (5). Pools were tested for Rickettsia spp. using real-time PCR. For positive samples multilocus sequence typing (MLST) was performed. Results The calculated minimum infection rate (MIR) for rickettsiae in the investigated ticks in Almaty region varied between 0.4–15.1% and 12.6–22.7% in the Kyzylorda region. At least four different Rickettsia species were identified in the two selected regions of Kazakhstan. Two of these are already known to science: Rickettsia raoultii and R. slovaca , the latter being reported for the first time in Almaty region One new form, “ Candidatus R. yenbekshikazakhensis”, was described by MLST of six gene fragments in Almaty region and one new genotype, “genotype R. talgarensis” was detected using three gene fragments. Conclusions Kazakh physicians should be aware of rickettsioses after tick bites in both regions studied. Both, R. raoultii and R. slovaca should be included in the diagnostics. The role for human diseases has further to be investigated for the newly described rickettsiae, “ Candidatus R. yenbekshikazakhensis” and “Genotype R. talgarensis”.
IntroductionC‐kit/SCF signaling plays a key role in regulating NK cell homeostasis, maturation, proliferation, and cytotoxicity. C‐kit‐deficiency in NK cells results in significant reduction of their number, suggesting an imperative role for c‐kit signaling in NK cell biology. We have recently showed that human NK cells express not only c‐kit‐receptor, but also both membrane‐bound and soluble forms of c‐kit ligand—Stem cell factor. The goal of this study was to characterize the c‐kit/SCF autocrine loop in peripheral blood NK cells obtained from patients with cancer.MethodsUsing Smart Flare and qRT‐PCR, we have characterized expression of c‐kit and two forms of SCF in patients’ NK cells and correlated these results with the expression of c‐myc and STAT3.ResultsOur results demonstrated that the expression of proto‐oncogenes c‐myc and c‐kit was significantly decreased in NK cells from all cancer patients. Expression of membrane‐bound SCF in NK cells correlated with the presence of remote metastases.ConclusionsWe suggest that the abnormal signaling and expression of c‐kit/SCF, c‐myc, and STAT3 in NK cells is responsible for the defect in their cytolytic activity in cancer and these defects at the gene expression level may be the cause rather than the result of tumor progression.
This study evaluated the efficiency of two biofilter systems, with and without biochar chambers installed, at degrading and removing HCH and its isomers in natural drainage water. The biochar biofilter proved to be 96% efficient at cleaning HCH and its transformation products from drainage water, a significant improvement over classic biofilter that remove, on average, 68% of HCH. Although iron- and sulfur-oxidizing bacteria, such as Gallionella and Sulfuricurvum, were dominant in the biochar bed outflows, they were absent in sediments, which were rich in Simplicispira, Rhodoluna, Rhodoferax, and Flavobacterium. The presence of functional genes involved in the biodegradation of HCH isomers and their byproducts was confirmed in both systems. The high effectiveness of the biochar biofilter displayed in this study should further encourage the use of biochar in water treatment solutions, e.g., for temporary water purification installations during the construction of other long-term wastewater treatment technologies, or even as final solutions at contaminated sites.
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