Epithelial-mesenchymal (EMT) and mesenchymal-epithelial (MET) transitions occur in the development of human tumorigenesis and are part of the natural history of the process to adapt to the changing ...microenvironment. In this setting, the miR-200 family is recognized as a master regulator of the epithelial phenotype by targeting ZEB1 and ZEB2, two important transcriptional repressors of the cell adherence (E-cadherin) and polarity (CRB3 and LGL2) genes. Recently, the putative DNA methylation associated inactivation of various miR-200 members has been described in cancer. Herein, we show that the miR-200ba429 and miR-200c141 transcripts undergo a dynamic epigenetic regulation linked to EMT or MET phenotypes in tumor progression. The 5'-CpG islands of both miR-200 loci were found unmethylated and coupled to the expression of the corresponding miRNAs in human cancer cell lines with epithelial features, such as low levels of ZEB1/ZEB2 and high expression of E-cadherin, CRB3 and LGL2, while CpG island hypermethylation-associated silencing was observed in transformed cells with mesenchymal characteristics. The recovery of miR-200ba429 and miR-200c141 expression by stable transfection in the hypermethylated cells restored the epithelial markers and inhibited migration in cell culture and tumoral growth and metastasis formation in nude mice. We also discovered, using both cell culture and animal models, that the miR-200 epigenetic silencing is not an static and fixed process but it can be shifted to hypermethylated or unmethylated 5'-CpG island status corresponding to the EMT and MET phenotypes, respectively. In fact, careful laser microdissection in human primary colorectal tumorigenesis unveiled that in normal colon mucosa crypts (epithelia) and stroma (mesenchyma) already are unmethylated and methylated at these loci, respectively; and that the colorectal tumors undergo selective miR-200 hypermethylation of their epithelial component. These findings indicate that the epigenetic silencing plasticity of the miR-200 family contributes to the evolving and adapting phenotypes of human tumors.
Plant–pollinator interactions are highly relevant to society as many crops important for humans are animal pollinated. However, changes in climate and land use may put such interacting patterns at ...risk by disrupting the occurrences between pollinators and the plants they pollinate. Here, we analyse how the co‐occurrence patterns between bat pollinators and 126 plant species they pollinate may be disrupted given changes in climate and land use, and we forecast relevant changes of the current bat–plant co‐occurrence distribution patterns for the near future. We predict under RCP8.5 21% of the territory will experience a loss of bat species richness, plants with C3 metabolism are predicted to reduce their area of distribution by 6.5%, CAM species are predicted to increase their potential area of distribution up to 1% and phanerophytes are predicted to have a 14% reduction in their distribution. The potential bat–plant interactions are predicted to decrease from an average of 47.1 co‐occurring bat–plant pairs in the present to 34.1 in the pessimistic scenario. The overall changes in suitable environmental conditions for bats and the plant species they pollinate may disrupt the current bat–plant co‐occurrence network and will likely put at risk the pollination services bat species provide.
Changes in climate and land use put plant–pollinator interactions at risk by disrupting their distribution patterns. We show that in the worst‐case climatic scenario, 21% of the Mexican territory, a biodiversity hotspot, will experience a loss of bat species richness. The potential bat–plant interactions are predicted to decrease from an average of 47.1 co‐occurring bat–plant pairs in the present to 34.1 in the pessimistic scenario. The overall changes in environmental conditions may disrupt the current bat–plant co‐occurrence network and will likely putt at risk the pollination services bat species provide.
The landscape of cancer treatment has dramatically changed over the last four decades. The age when surgery and radiotherapy were the only effective way to fight tumour growth has ended. A complex ...scenario where the molecular features of tumours seem to be the cornerstone of any therapy is now emerging. Here we provide an overview on the different approaches to cancer treatment. This review will help the reader to acknowledge the pivotal role of some classic cancer therapies, including surgery, radiation, chemotherapy and endocrine therapy, now better understood in the mechanims underpinning their efficacy. Following, we focus on the understanding of the value of systemic treatment and on an up-date on the novel, up-coming therapies of the current targeted therapy age, including new antibodies, small molecules, antiangiogenics and viral therapy. We briefly elaborate, finally, on new biomarkers development and how it should rule and determine the future of therapeutic research in cancer.
Intensity of tennis match play Fernandez, J; Mendez-Villanueva, A; Pluim, B M
British Journal of Sports Medicine,
05/2006, Letnik:
40, Številka:
5
Journal Article, Book Review
Recenzirano
Odprti dostop
This review focuses on the characteristics of tennis players during match play and provides a greater insight into the energy demands of tennis. A tennis match often lasts longer than an hour and in ...some cases more than five hours. During a match there is a combination of periods of maximal or near maximal work and longer periods of moderate and low intensity activity. Match intensity varies considerably depending on the players’ level, style, and sex. It is also influenced by factors such as court surface and ball type. This has important implications for the training of tennis players, which should resemble match intensity and include interval training with appropriate work to rest ratios.
Photodynamic therapy (PDT) is a clinically approved therapeutic modality for the treatment of diseases characterized by uncontrolled cell proliferation, mainly cancer. It involves the selective ...uptake of a photosensitizer (PS) by neoplastic tissue, which is able to produce reactive oxygen species upon irradiation with light, leading to tumor regression. Here a synergistic cell photoinactivation is reported based on the simultaneous administration of two PSs, zinc(II)-phthalocyanine (ZnPc) and the cationic porphyrin meso-tetrakis(4-N-methylpyridyl)porphine (TMPyP) in three cell lines (HeLa, HaCaT and MCF-7), using very low doses of PDT. We detected changes from predominant apoptosis (without cell detachment) to predominant necrosis, depending on the light dose used (2.4 and 3.6 J/cm(2), respectively). Analysis of changes in cytoskeleton components (microtubules and F-actin), FAK protein, as well as time-lapse video microscopy evidenced that HeLa cells were induced to undergo apoptosis, without losing adhesion to the substrate. Moreover, 24 h after intravenous injection into tumor-bearing mice, ZnPc and TMPyP were preferentially accumulated in the tumor area. PDT with combined treatment produced significant retardation of tumor growth. We believe that this combined and highly efficient strategy (two PSs) may provide synergistic curative rates regarding conventional photodynamic treatments (with one PS alone).
The coding and promoter region sequences from the BiP-like protein SBiP1 from Symbiodinium microadriaticum CassKB8 were obtained by PCR, sequenced and compared with annotated sequences. The ...nucleotides corresponding to the full sequence were correctly annotated and the main SBiP1 features determined at the nucleotide and amino acid level. The translated protein was organized into the typical domains of the BiP/HSP70 family including a signal peptide, a substrate- and a nucleotide-binding domain, and an ER localization sequence. Conserved motifs included a highly conserved Thr513 phosphorylation site and two ADP-ribosylation sites from eukaryotic BiP's. Molecular modeling showed the corresponding domain regions and main exposed post-translational target sites in its three-dimensional structure, which also closely matched Homo sapiens BiP further indicating that it indeed corresponds to a BiP/HSP70 family protein. The gene promoter region showed at least eight light regulation-related sequences consistent with the molecule being highly phosphorylated in Thr under dark conditions and dephosphorylated upon light stimuli. We tested light parameter variations that could modulate the light mediated phosphorylation effect and found that SBiP1 Thr dephosphorylation was only significantly detected after 15-30 min light stimulation. Such light-induced dephosphorylation was observed even when dichlorophenyl dimethyl urea, a photosynthesis inhibitor, was also present in the cells during the light stimulation. Dephosphorylation occurred indistinctly under red, yellow, blue or the full visible light spectra. In additon, it was observed at a light intensity of as low as 1 mumole photon m.sup.-2 s.sup.-1 . Our results indicate that: a) SBiP1 is a chaperone belonging to the BiP/HSP70 family proteins; b) its light-modulated phosphorylation/dephosphorylation most likely functions as an activity switch for the chaperone; c) this light-induced modulation occurs relatively slow but is highly sensitive to the full spectrum of visible light; and d) the light induced Thr dephosphorylation is independent of photosynthetic activity in these cells.
Measles virus (MeV) is a paramyxovirus that infects humans, principally children. Despite the existence of an effective and safe vaccine, the number of cases of measles has increased due to lack of ...vaccination coverage. The World Health Organization (WHO) reports that the number of cases worldwide multiplied fourfold between January and March 2019, to 112,000. Today, there is no treatment available for MeV. In recent years, it has been demonstrated that natural extracts (herbal or algal) with antiviral activity can also work as reducing agents that, in combination with nanotechnology, offer an innovative option to counteract viral infections. Here, we synthetized and evaluated the antiviral activity of gold nanoparticles using garlic extract (
) as a reducing agent (AuNPs-As). These nanoparticles actively inhibited MeV replication in Vero cells at a 50% effective concentration (EC
) of 8.829 µg/mL, and the selectivity index (SI) obtained was 16.05. AuNPs-As likely inhibit viral infection by blocking viral particles directly, showing a potent virucidal effect. Gold nanoparticles may be useful as a promising strategy for treating and controlling the infection of MeV and other related enveloped viruses.
The activity profiles of highly trained young soccer players were examined in relation to age, playing position and physical capacity. Time-motion analyses (global positioning system) were performed ...on 77 (U13-U18; fullbacks FB, centre-backs CB, midfielders MD, wide midfielders W, second strikers 2 (nd)S and strikers S) during 42 international club games. Total distance covered (TD) and very high-intensity activities (VHIA; >16.1 km·h (-1)) were computed during 186 entire player-matches. Physical capacity was assessed via field test measures (e. g., peak running speed during an incremental field test, VVam-eval). Match running performance showed an increasing trend with age ( P<0.001, partial eta-squared (η (2)): 0.20-0.45). When adjusted for age and individual playing time, match running performance was position-dependent ( P<0.001, η (2): 0.13-0.40). MD covered the greater TD; CB the lowest ( P<0.05). Distance for VHIA was lower for CB compared with all other positions ( P<0.05); W and S displayed the highest VHIA ( P<0.05). Relationships between match running performance and physical capacities were position-dependent, with poor or non-significant correlations within FB, CB, MD and W (e. g., VHIA vs. VVam-eval: R=0.06 in FB) but large associations within 2 (nd)S and S positions (e. g., VHIA vs. VVam-eval: R=0.70 in 2 (nd)S). In highly trained young soccer players, the importance of fitness level as a determinant of match running performance should be regarded as a function of playing position.
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