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41.
Marta Teixeira Pinto Ana Sofia Ribeiro Inês Conde Rita Carvalho Joana Paredes 《International journal of molecular sciences》2021,22(1)
The high plasticity of cancer stem-like cells (CSCs) allows them to differentiate and proliferate, specifically when xenotransplanted subcutaneously into immunocompromised mice. CSCs are highly tumorigenic, even when inoculated in small numbers. Thus, in vivo limiting dilution assays (LDA) in mice are the current gold standard method to evaluate CSC enrichment and activity. The chick embryo chorioallantoic membrane (CAM) is a low cost, naturally immune-incompetent and reproducible model widely used to evaluate the spontaneous growth of human tumor cells. Here, we established a CAM-LDA assay able to rapidly reproduce tumor specificities—in particular, the ability of the small population of CSCs to form tumors. We used a panel of organotropic metastatic breast cancer cells, which show an enrichment in a stem cell gene signature, enhanced CD44+/CD24−/low cell surface expression and increased mammosphere-forming efficiency (MFE). The size of CAM-xenografted tumors correlate with the number of inoculated cancer cells, following mice xenograft growth pattern. CAM and mice tumors are histologically comparable, displaying both breast CSC markers CD44 and CD49f. Therefore, we propose a new tool for studying CSC prevalence and function—the chick CAM-LDA—a model with easy handling, accessibility, rapid growth and the absence of ethical and regulatory constraints. 相似文献
42.
Rosa Maria Paragliola Andrea Corsello Giampaolo Papi Alfredo Pontecorvi Salvatore Maria Corsello 《International journal of molecular sciences》2021,22(6)
The most known effects of endogenous Cushing’s syndrome are the phenotypic changes and metabolic consequences. However, hypercortisolism can exert important effects on other endocrine axes. The hypothalamus–pituitary–thyroid axis activity can be impaired by the inappropriate cortisol secretion, which determinates the clinical and biochemical features of the “central hypothyroidism”. These findings have been confirmed by several clinical studies, which also showed that the cure of hypercortisolism can determine the recovery of normal hypothalamus–pituitary–thyroid axis activity. During active Cushing’s syndrome, the “immunological tolerance” guaranteed by the hypercortisolism can mask, in predisposed patients, the development of autoimmune thyroid diseases, which increases in prevalence after the resolution of hypercortisolism. However, the immunological mechanism is not the only factor that contributes to this phenomenon, which probably includes also deiodinase-impaired activity. Cushing’s syndrome can also have an indirect impact on thyroid function, considering that some drugs used for the medical control of hypercortisolism are associated with alterations in the thyroid function test. These considerations suggest the utility to check the thyroid function in Cushing’s syndrome patients, both during the active disease and after its remission. 相似文献
43.
Leticia B. Rosa Rochanna L. Aires Laiane S. Oliveira Josielle V. Fontes Prof. Danilo C. Miguel Prof. Camilla Abbehausen 《ChemMedChem》2021,16(11):1682-1696
Leishmaniasis is one of the most neglected diseases worldwide and is considered a serious public health issue. The current therapeutic options have several disadvantages that make the search for new therapeutics urgent. Gold compounds are emerging as promising candidates based on encouraging in vitro and limited in vivo results for several AuI and AuIII complexes. The antiparasitic mechanisms of these molecules remain only partially understood. However, a few studies have proposed the trypanothione redox system as a target, similar to the mammalian thioredoxin system, pointed out as the main target for several gold compounds with significant antitumor activity. In this review, we present the current status of the investigation and design of gold compounds directed at treating leishmaniasis. In addition, we explore potential targets in Leishmania parasites beyond the trypanothione system, taking into account previous studies and structure modulation performed for gold-based compounds. 相似文献
44.
Roberta Squecco Alessia Tani Flaminia Chellini Rachele Garella Eglantina Idrizaj Irene Rosa Sandra Zecchi-Orlandini Mirko Manetti Chiara Sassoli 《International journal of molecular sciences》2021,22(7)
Bone marrow-mesenchymal stem/stromal cells (MSCs) may offer promise for skeletal muscle repair/regeneration. Growing evidence suggests that the mechanisms underpinning the beneficial effects of such cells in muscle tissue reside in their ability to secrete bioactive molecules (secretome) with multiple actions. Hence, we examined the effects of MSC secretome as conditioned medium (MSC-CM) on ex vivo murine extensor digitorum longus muscle injured by forced eccentric contraction (EC). By combining morphological (light and confocal laser scanning microscopies) and electrophysiological analyses we demonstrated the capability of MSC-CM to attenuate EC-induced tissue structural damages and sarcolemnic functional properties’ modifications. MSC-CM was effective in protecting myofibers from apoptosis, as suggested by a reduced expression of pro-apoptotic markers, cytochrome c and activated caspase-3, along with an increase in the expression of pro-survival AKT factor. Notably, MSC-CM also reduced the EC-induced tissue redistribution and extension of telocytes/CD34+ stromal cells, distinctive cells proposed to play a “nursing” role for the muscle resident myogenic satellite cells (SCs), regarded as the main players of regeneration. Moreover, it affected SC functionality likely contributing to replenishment of the SC reservoir. This study provides the necessary groundwork for further investigation of the effects of MSC secretome in the setting of skeletal muscle injury and regenerative medicine. 相似文献
45.
Lucia Garcia-Garcia Laia Olle Margarita Martin Jordi Roca-Ferrer Rosa Muoz-Cano 《International journal of molecular sciences》2021,22(10)
Adenosine is a nucleoside involved in the pathogenesis of allergic diseases. Its effects are mediated through its binding to G protein-coupled receptors: A1, A2a, A2b and A3. The receptors differ in the type of G protein they recruit, in the effect on adenylyl cyclase (AC) activity and the downstream signaling pathway triggered. Adenosine can produce both an enhancement and an inhibition of mast cell degranulation, indicating that adenosine effects on these receptors is controversial and remains to be clarified. Depending on the study model, A1, A2b, and A3 receptors have shown anti- or pro-inflammatory activity. However, most studies reported an anti-inflammatory activity of A2a receptor. The precise knowledge of the adenosine mechanism of action may allow to develop more efficient therapies for allergic diseases by using selective agonist and antagonist against specific receptor subtypes. 相似文献
46.
Rodrigo F. Ortiz-Meoz Liping Wang Rosalie Matico Anna Rutkowska-Klute Martha De la Rosa Sabrina Bedard Robert Midgett Katrin Strohmer Douglas Thomson Cunyu Zhang Makda Mebrahtu Jeffrey Guss Rachel Totoritis Thomas Consler Nino Campobasso David Taylor Tia Lewis Kurt Weaver Marcel Muelbaier John Seal Richard Dunham Wieslaw Kazmierski David Favre Giovanna Bergamini Lisa Shewchuk Alan Rendina Guofeng Zhang 《Chembiochem : a European journal of chemical biology》2021,22(3):516-522
Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism. As it is an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of IDO1 inhibitors with various mechanisms of inhibition is of great interest. Comparison of an apo-form-binding IDO1 inhibitor (GSK5628) to the heme-coordinating compound, epacadostat (Incyte), allows us to explore the details of the apo-binding inhibition of IDO1. Herein, we demonstrate that GSK5628 inhibits IDO1 by competing with heme for binding to a heme-free conformation of the enzyme (apo-IDO1), whereas epacadostat coordinates its binding with the iron atom of the IDO1 heme cofactor. Comparison of these two compounds in cellular systems reveals a long-lasting inhibitory effect of GSK5628, previously undescribed for other known IDO1 inhibitors. Detailed characterization of this apo-binding mechanism for IDO1 inhibition might help design superior inhibitors or could confer a unique competitive advantage over other IDO1 inhibitors vis-à-vis specificity and pharmacokinetic parameters. 相似文献
47.
C. Tuve' R. Potenza M. Chiorboli M.G. Grimaldi F. La Rosa F. Raimondo M. Marinelli E. Milani A. Tucciarone G. Verona Rinati M. Donato G. Faggio G. Messina S. Santangelo G. Pucella 《Diamond and Related Materials》2006,15(11-12):1986
Polycrystalline (pCVD) and single crystal (scCVD) diamond films grown from Chemical Vapour Deposition (CVD), if sufficiently pure at Raman analysis, are very good materials for beam or flux monitors inside accelerators or nuclear reactors. This is because they are very hard to damage in high radiation fields and very resistant to high temperatures. Films of pCVD diamond are, however, not so good as spectroscopy detectors due to inhomogeneities induced by their growth in grains with the consequent presence of grain boundaries which worsen their energy resolution. The latter can be significantly improved by growing scCVD diamond films onto HPHT synthetic diamond substrates. We have shown that it is possible to measure the density of defects inside diamond specimens using as probes suitable penetrating nuclear radiations. With the preliminary results reported here we'll show that, bombarding CVD diamond films grown at Roma “Tor Vergata” with energetic protons and 4He, 6Li and 12C ions produced in the accelerators of Catania laboratories, the pulse height defects are higher than those in silicon detectors and likewise well described by a power law in the deposited energy. Furthermore, we'll show that pulse heights for the same particles seem to depend on the duration of the measurement, thus exhibiting a sort of depolarization of the insulator when exposed to the electric voltage which makes it a particle detector. 相似文献
48.
D. S. Rosa I. Chiovatto Neto M. R. Calil A. G. Pedroso C. P. Fonseca S. Neves 《应用聚合物科学杂志》2004,91(6):3909-3914
The thermal and mechanical properties of low‐density polyethylene (LDPE), poly(ε‐caprolactone) (PCL), and their blends were evaluated. Differential scanning calorimetry showed that increasing the PCL content of the blend did not change the LDPE melting temperature, but reduced the crystallinity by up to 16.8%. This behavior was related to interactions between the PCL chains and the crystalline phase of LDPE. Tensile strength and elongation at break values for the blends were lower than those for the pure polymers, which suggested an incompatibility between the polymers. The values for Young's modulus under tensile increased when PCL was added to LDPE. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 91:3909–3914, 2004 相似文献
49.
Méndez RO Bueno K Campos N López D Wyatt CJ Ortega MI 《Archivos latinoamericanos de nutrición》2005,55(2):187-193
Developing countries diets are based on a variety of plant foods that often are the main suppliers of important amounts of iron (Fe) and zinc (Zn). The objectives of this study were 1) to measure the total and dialyzable amounts of Fe and Zn in foods from Northern Mexico (Sonora) and from Southern Mexico (Oaxaca) and 2) to evaluate the effect of meat content of diets on the dialyzable amount of Fe and Zn. Methods to calculate the total dialyzable amount of Fe and Zn, were those of the AOAC and of Shen et al. Total Fe in e northern Mexican foods went from 0.78 +/- 0.0 to 11.59 +/- to 0.03 mg/ 100g (dry weight, DW); in southern Mexican foods the same micronutrient amounts were 0.86 +/- 0.18 to 8.8 +/- 0.57 mg/100 g (BS). Total Zn values were 0.91 +/- 0.00 to 13.58 +/- 0.05 mg/100 g (DW) in Sonora, and 0.64 +/- 0.18 to 20.80 +/- 0.33 mg/100 g (DW) in Oaxaca. In northern Mexico, foods dialyzable Fe had values from 0.1 +/- 0.04% to 10.6 +/- 0.36% and for Zn from 4.0 +/- 0.21% to 55.32 +/- 0.14%. Meanwhile, the range of values of dialyzable Fe for foods from Oaxaca were from 0.22 +/- 0.06% to 9.40 +/- 0.14% for and from 2.41 +/- 0.26% to 54.27 +/- 1.49% for dialyzable Zn. The average value for dialyzable Fe was higher in the foods that contained meat or meat products (p= 0.001). 相似文献
50.
J.R.F.Guedes de Carvalho 《Chemical engineering science》1981,36(8):1349-1356
A theory for slug stability in fluidised beds of fine particles is developed based on the idea of gas circulation inside bubbles.Data on the intensity of circulation inside gas slugs in liquids are reported and an analogy is drawn with slugs in fluidised beds; this information is coupled with data on gas pick-up velocity for flow over granular beds, to yield a simple criterion for slug stability. A test of this criterion is provided by comparison with data on the stability of freely slugging beds.An X-ray study of slugs in fluidised beds at various pressures is also described that gives further support to the predictions of the theory. 相似文献