1. elektronické vydání 1 online zdroj (242 stran)
Další - již osmá - studie z ediční řady Školní vzdělávání v zahraničí analyzuje vzdělávací systém nejlidnatější země světa - Číny. V testech PISA obsazují v mezinárodním srovnání čínští žáci přední příčky. Co však stojí za tímto úspěchem? A jaké jsou jeho odvrácené stránky? Autoři snaží nabídnout komplexní odpovědi na tyto i jiné významné otázky spojené právě se vzděláváním v Číně. V úvodních kapitolách je proto představen zeměpisný, historický, náboženský a ekonomický kontext, na nějž navazují věcné analýzy vzdělávací politiky, kurikula a dalších aspektů školního vzdělávání. Kniha tak osloví nejen čtenáře se zájmem o pedagogiku, ale i širší okruh čtenářů z řad diplomacie, kultury, politiky či obchodu, kteří se zajímají o edukační zázemí svých partnerů a klientů.
Skeletal muscle atrophy is associated with a loss of muscle protein which may result from both increased proteolysis and decreased protein synthesis. Investigations on cell signaling pathways that regulate muscle atrophy have promoted our understanding of this complicated process. Emerging evidence implicates that calpains play key roles in dysregulation of proteolysis seen in muscle atrophy. Moreover, studies have also shown that abnormally activated calpain results muscle atrophy via its downstream effects on ubiquitin-proteasome pathway (UPP) and Akt phosphorylation. This review will discuss the role of calpains in regulation of skeletal muscle atrophy mainly focusing on its collaboration with either UPP or Akt in atrophy conditions in hope to stimulate the interest in development of novel therapeutic interventions for skeletal muscle atrophy.
- MeSH
- Hypertrophy MeSH
- Receptor Cross-Talk MeSH
- Calpain metabolism MeSH
- Humans MeSH
- Proteasome Endopeptidase Complex metabolism MeSH
- Proteolysis * MeSH
- Proto-Oncogene Proteins c-akt metabolism MeSH
- Signal Transduction MeSH
- Muscular Atrophy metabolism MeSH
- Muscle Proteins metabolism MeSH
- Ubiquitin metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Cryptococcus neoformans is an opportunistic fungal pathogen that can cause life-threatening invasive fungal infections. As its prevalence and drug resistance continue to rise, cryptococcosis requires new treatment options. Tapping into the potential antifungal effects of traditional drugs or combination therapy has become one of the options. This study was the first to examine the interaction of hydroxychloroquine (HCQ) and itraconazole (ITR) on Cryptococcus neoformans in vitro and in vivo. Our results showed that HCQ alone and in combination with ITR exhibited antifungal activity against C. neoformans planktonic cells. When HCQ was combined with ITR, the minimal inhibitory concentration (MIC) value of HCQ decreased to 32 μg/mL, and the MIC value of ITR decreased from 0.25 μg/mL to 0.06-0.25 μg/mL. The time-killing curve showed that the combined application of HCQ and ITR significantly shortened the killing time, dynamically defining the antifungal activity. The minimum biofilm clearance concentration (MBEC) of HCQ was only 32 μg/mL, which was significantly lower than the MIC of HCQ for planktonic cells. When combined with ITR, the MBEC of ITR decreased from 128 μg/mL to 2-1 μg/mL, and the MBEC of HCQ decreased from 32 μg/mL to 4 μg/mL, indicating a synergistic antifungal biofilm effect. In comparison to ITR alone, the combination of HCQ and ITR treatment increased the survival of C. neoformans-infected Galleria mellonella larvae and decreased the fungal burden of infected larvae. Mechanistic investigations revealed that HCQ might damage C. neoformans cell membranes, impact the structure of fungal cells, cause extracellular material leakage, and have a potent affinity for attaching to the C. neoformans genomic DNA. In conclusion, HCQ has potential clinical application in the treatment of cryptococcosis.
- MeSH
- Antifungal Agents pharmacology therapeutic use MeSH
- Cryptococcus neoformans * MeSH
- Hydroxychloroquine pharmacology therapeutic use MeSH
- Itraconazole pharmacology MeSH
- Cryptococcosis * drug therapy microbiology MeSH
- Microbial Sensitivity Tests MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
Oxidored-nitro domain-containing protein 1 (NOR1) is a critical tumour suppressor gene, though its regulatory mechanism in oxidative stress of glioblastoma (GBM) remains unclear. Hence, further study is needed to unravel the function of NOR1 in the progression of oxidative stress in GBM. In this study, we evaluated the expression of NOR1 and nuclear respiratory factor 1 (NRF1) in GBM tissue and normal brain tissue (NBT) using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB), and investigated their relationship. We then induced oxidative stress in U251 cells through H2O2 treatment and conducted Cell Count-ing Kit-8, Transwell and wound healing assays to analyse cell proliferation, invasion and migration. Cell apoptosis was assessed by flow cytometry and TUNEL staining. We also measured the activities of superoxide dismutase and catalase, as well as the level of reactive oxygen species (ROS) using biochemical techniques. Via qRT-PCR and WB, the mRNA and protein expression levels of NOR1 and NRF1 were determined. Chromatin immunoprecipitation (ChIP) assays were applied to validate NRF1's interaction with NOR1. Our results showed that the expression of NOR1 and NRF1 was low in GBM, and their expression levels were positively correlated. H2O2-induced oxidative stress reduced NRF1 and NOR1 expression levels and increased the ROS level. The ChIP assay confirmed the binding of NRF1 to NOR1. Over-expression of NRF1 attenuated the inhibitory effect of oxidative stress on the proliferation, migration and invasion of U251 cells, which was reversed by knockdown of NOR1.
Hypoxia-inducible factor-1alpha (HIF-1alpha) transcriptionally regulates expression of several target genes in protecting tissues against hypoxia. With hypoxic stress, vascular endothelial growth factor (VEGF) is a signal protein produced by cells and further contributes to improvement of vascular functions and restoring the oxygen supply to tissues. In this current study, we first hypothesized that the protein levels of HIF-1alpha and VEGF are reduced in skeletal muscles of plateau animals [China Qinghai-Tibetan plateau pikas (ochotona curzoniae)] in response to hypoxia as compared with control animals [normal lowland Sprague-Dawley (SD) rats]. We further hypothesized that HIF-1alpha plays a role in regulating expression of VEGF in skeletal muscle. Note that HIF-1alpha and VEGF were determined by using two-site immunoenzymatic assay (ELISA) methods. Our results demonstrated that hypoxic stress induced by exposure of lower O(2) (6 h) significantly increased the levels of HIF-1alpha and VEGF in the oxidative and glycolytic muscles of SD rats and pikas (P<0.05 vs. normoxic conditions). Notably, the increases in HIF-1alpha and VEGF were significantly less in pikas (P<0.05, vs. SD controls) than in SD rats. In addition, a linear relationship was observed between amplified HIF-1alpha and VEGF in oxidative muscle (r=0.76 and P<0.01) and glycolytic muscle (r=0.72 and P<0.01) and inhibiting HIF-1alpha significantly decreased expression of VEGF induced by hypoxic stress in skeletal muscles (P<0.05). Overall, our findings suggest that (1) responsiveness of HIF-1alpha and VEGF in skeletal muscles to hypoxic stress is blunted in plateau animals, and (2) HIF-1alpha has a regulatory effect on VEGF under hypoxic environment.
- MeSH
- Hypoxia-Inducible Factor 1, alpha Subunit biosynthesis MeSH
- Hypoxia metabolism MeSH
- Muscle, Skeletal metabolism MeSH
- Rats MeSH
- Lagomorpha metabolism MeSH
- Rats, Sprague-Dawley MeSH
- Vascular Endothelial Growth Factor A biosynthesis MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Microsporidia are intracellular parasites of insects and other higher eukaryotes. The microsporidian Nosema philosamiae Talukdar, 1961 was isolated from the eri silkworm, Philosamia cynthia ricini Grote. In the present study, alpha- and beta-tubulin genes from N. philosamiae were characterized. The identity analysis of nucleotide and amino acid sequences indicated high similarity with species of Nosema Nägeli, 1857 sensu lato (nucleotide sequences, > or = 96.0%; amino acid sequences, > or = 99.0%). However, the tubulin genes of N. philosamiae share low sequence similarity with that of N. ceranae Fries, Feng, da Silva, Slemenda et Pieniazek, 1996 (strain BRL01) and a Nosema/Vairimorpha species. Phylogenies based on alpha-, beta- and combined alpha- plus beta-tubulin gene sequences showed that N. philosamiae, along with the true Nosema species, forms a separate clade with a high bootstrap value, with N. ceranae BRL01 forming a clade of its own. The results indicated that the alpha- and beta-tubulin sequences may be useful as a diagnostic tool to discriminate the true Nosema group from the Nosema/Vairimorpha group.
Parkinson's disease (PD) is a neurodegenerative disease with a progressive loss of mesencephalic dopaminergic neurons of the substantia nigra (SN). To further evaluate its pathophysiology, accurate animal models are needed. The current study aims to verify the impact of a 6-hydroxydopamine (6-OHDA) bilateral microinjection into the SN on gastrointestinal symptoms in rats and confirm that the 6-OHDA rat model is an appropriate tool to investigate the mechanisms of Parkinsonian GI disorders. Immunohistochemistry, digital X-ray imaging, short-circuit current, FITC-dextran permeability and ultra-performance liquid chromatography tandem mass spectrometry were used in this study. The results indicated that the dopaminergic neurons in SN and fibres in the striatum were markedly reduced in 6-OHDA rats. The 6-OHDA rats manifested reductions in occupancy in a rotarod test and increases in daily food debris but no difference in body mass or daily consumption. Compared with control rats, faecal pellets and their contents were significantly decreased, whereas gastric emptying and intestinal transport were delayed in 6-OHDA rats. The increased in vivo FITC-dextran permeability and decreased intestinal transepithelial resistance in the model suggest attenuated barrier function in the digestive tract in the PD model. Moreover, inflammatory factors in the plasma showed that pro-inflammatory factors IL-1? and IL-8 were significantly increased in 6-OHDA rats. Collectively, these findings indicate that the model is an interesting experimental tool to investigate the mechanisms involved in the progression of gastrointestinal dysfunction in PD.
- MeSH
- Gastrointestinal Diseases chemically induced diagnostic imaging physiopathology MeSH
- Rats MeSH
- Oxidopamine toxicity MeSH
- Parkinsonian Disorders chemically induced diagnostic imaging physiopathology MeSH
- Rats, Sprague-Dawley MeSH
- Sympatholytics toxicity MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Subjective cognitive decline (SCD) may serve as a symptomatic indicator for preclinical Alzheimer's disease; however, SCD is a heterogeneous entity regarding clinical progression. We aimed to investigate whether spatial navigation could reveal subcortical structural alterations and the risk of progression to objective cognitive impairment in SCD individuals. METHODS: One hundred and eighty participants were enrolled: those with SCD (n = 80), normal controls (NCs, n = 77), and mild cognitive impairment (MCI, n = 23). SCD participants were further divided into the SCD-good (G-SCD, n = 40) group and the SCD-bad (B-SCD, n = 40) group according to their spatial navigation performance. Volumes of subcortical structures were calculated and compared among the four groups, including basal forebrain, thalamus, caudate, putamen, pallidum, hippocampus, amygdala, and accumbens. Topological properties of the subcortical structural covariance network were also calculated. With an interval of 1.5 years ± 12 months of follow-up, the progression rate to MCI was compared between the G-SCD and B-SCD groups. RESULTS: Volumes of the basal forebrain, the right hippocampus, and their respective subfields differed significantly among the four groups (p < 0.05, false discovery rate corrected). The B-SCD group showed lower volumes in the basal forebrain than the G-SCD group, especially in the Ch4p and Ch4a-i subfields. Furthermore, the structural covariance network of the basal forebrain and right hippocampal subfields showed that the B-SCD group had a larger Lambda than the G-SCD group, which suggested weakened network integration in the B-SCD group. At follow-up, the B-SCD group had a significantly higher conversion rate to MCI than the G-SCD group. CONCLUSION: Compared to SCD participants with good spatial navigation performance, SCD participants with bad performance showed lower volumes in the basal forebrain, a reorganized structural covariance network of subcortical nuclei, and an increased risk of progression to MCI. Our findings indicated that spatial navigation may have great potential to identify SCD subjects at higher risk of clinical progression, which may contribute to making more precise clinical decisions for SCD individuals who seek medical help.
