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91.
Olga Azevedo Filipa Cordeiro Miguel Fernandes Gago Gabriel Miltenberger-Miltenyi Catarina Ferreira Nuno Sousa Damio Cunha 《International journal of molecular sciences》2021,22(9)
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene that result in a deficiency of the enzymatic activity of α-galactosidase A and consequent accumulation of glycosphingolipids in body fluids and lysosomes of the cells throughout the body. GB3 accumulation occurs in virtually all cardiac cells (cardiomyocytes, conduction system cells, fibroblasts, and endothelial and smooth muscle vascular cells), ultimately leading to ventricular hypertrophy and fibrosis, heart failure, valve disease, angina, dysrhythmias, cardiac conduction abnormalities, and sudden death. Despite available therapies and supportive treatment, cardiac involvement carries a major prognostic impact, representing the main cause of death in FD. In the last years, knowledge has substantially evolved on the pathophysiological mechanisms leading to cardiac damage, the natural history of cardiac manifestations, the late-onset phenotypes with predominant cardiac involvement, the early markers of cardiac damage, the role of multimodality cardiac imaging on the diagnosis, management and follow-up of Fabry patients, and the cardiac efficacy of available therapies. Herein, we provide a comprehensive and integrated review on the cardiac involvement of FD, at the pathophysiological, anatomopathological, laboratory, imaging, and clinical levels, as well as on the diagnosis and management of cardiac manifestations, their supportive treatment, and the cardiac efficacy of specific therapies, such as enzyme replacement therapy and migalastat. 相似文献
92.
Alberto Molares-Vila Alberte Corbaln-Rivas Miguel Carnero-Gregorio Jos Luís Gonzlez-Cespn Carmen Rodríguez-Cerdeira 《International journal of molecular sciences》2021,22(9)
Glycogen storage diseases (GSDs) are a group of 19 hereditary diseases caused by a lack of one or more enzymes involved in the synthesis or degradation of glycogen and are characterized by deposits or abnormal types of glycogen in tissues. Their frequency is very low and they are considered rare diseases. Except for X-linked type IX, the different types are inherited in an autosomal recessive pattern. In this study we reviewed the literature from 1977 to 2020 concerning GSDs, biomarkers, and metabolic imbalances in the symptoms of some GSDs. Most of the reported studies were performed with very few patients. Classification of emerging biomarkers between different types of diseases (hepatics GSDs, McArdle and PDs and other possible biomarkers) was done for better understanding. Calprotectin for hepatics GSDs and urinary glucose tetrasaccharide for Pompe disease have been approved for clinical use, and most of the markers mentioned in this review only need clinical validation, as a final step for their routine use. Most of the possible biomarkers are implied in hepatocellular adenomas, cardiomyopathies, in malfunction of skeletal muscle, in growth retardation, neutropenia, osteopenia and bowel inflammation. However, a few markers have lost interest due to a great variability of results, which is the case of biotinidase, actin alpha 2, smooth muscle, aorta and fibroblast growth factor receptor 4. This is the first review published on emerging biomarkers with a potential application to GSDs. 相似文献
93.
Ivn Benito Ignacio J. Encío Fermín I. Milagro María Alfaro Ana Martínez-Peuela Miguel Barajas Florencio Marzo 《International journal of molecular sciences》2021,22(9)
Recent studies have suggested that flavonoids such as quercetin and probiotics such as Bifidobacterium bifidum (Bf) and Lactobacillus gasseri (Lg) could play a relevant role in inhibiting colon cancer cell growth. Our study investigated the role of dietary supplementation with microencapsulated probiotics (Bf and Lg) along with quercetin in the development of mouse colorectal cancer (CRC). Methods: Adenomatous polyposis coli/multiple intestinal neoplasia (ApcMin/+) mice were fed a standard diet or the same diet supplemented with microencapsulated probiotics (Bf and Lg strains, 107 CFU/100 g food) or both probiotics strains plus microencapsulated quercetin (15 mg/100 g food) for 73 days. Changes in body and organ weights, energy metabolism, intestinal microbiota, and colon tissue were determined. The expression of genes related to the Wnt pathway was also analyzed in colon samples. Results: Dietary supplementation with microencapsulated probiotics or microencapsulated probiotics plus quercetin reduced body weight loss and intestinal bleeding in ApcMin/+ mice. An improvement in energy expenditure was observed after 8 weeks but not after 10 weeks of treatment. A supplemented diet with microencapsulated Bf and Lg reduced the number of aberrant crypt foci (ACF) and adenomas by 45% and 60%, respectively, whereas the supplementation with Bf, Lg and quercetin decreased the number of ACF and adenomas by 57% and 80%, respectively. Microencapsulated Bf and Lg in combination with quercetin could exert inhibition of the canonical Wnt/β-catenin signaling pathway in the colon of ApcMin/+ mice Conclusions: The administration of microencapsulated Bf and Lg, individually or in combination with quercetin, inhibits the CRC development in ApcMin/+ mice. 相似文献
94.
Pablo Bonilla Joaquim Hernandez Esther Giraldo Miguel A. Gonzlez-Prez Ana Alastrue-Agudo Hoda Elkhenany María J. Vicent Xavier Navarro Michael Edel Victoria Moreno-Manzano 《International journal of molecular sciences》2021,22(11)
We currently lack effective treatments for the devastating loss of neural function associated with spinal cord injury (SCI). In this study, we evaluated a combination therapy comprising human neural stem cells derived from induced pluripotent stem cells (iPSC-NSC), human mesenchymal stem cells (MSC), and a pH-responsive polyacetal–curcumin nanoconjugate (PA-C) that allows the sustained release of curcumin. In vitro analysis demonstrated that PA-C treatment protected iPSC-NSC from oxidative damage in vitro, while MSC co-culture prevented lipopolysaccharide-induced activation of nuclear factor-κB (NF-κB) in iPSC-NSC. Then, we evaluated the combination of PA-C delivery into the intrathecal space in a rat model of contusive SCI with stem cell transplantation. While we failed to observe significant improvements in locomotor function (BBB scale) in treated animals, histological analysis revealed that PA-C-treated or PA-C and iPSC-NSC + MSC-treated animals displayed significantly smaller scars, while PA-C and iPSC-NSC + MSC treatment induced the preservation of β-III Tubulin-positive axons. iPSC-NSC + MSC transplantation fostered the preservation of motoneurons and myelinated tracts, while PA-C treatment polarized microglia into an anti-inflammatory phenotype. Overall, the combination of stem cell transplantation and PA-C treatment confers higher neuroprotective effects compared to individual treatments. 相似文献
95.
Aintzane Rueda-Martínez Aiara Garitazelaia Ariadna Cilleros-Portet Sergi Marí Rebeca Arauzo Jokin de Miguel Brbara P. Gonzlez-García Nora Fernandez-Jimenez Jose Ramon Bilbao Iraia García-Santisteban 《International journal of molecular sciences》2021,22(11)
Endometriosis is a common gynecological disorder that has been associated with endometrial, breast and epithelial ovarian cancers in epidemiological studies. Since complex diseases are a result of multiple environmental and genetic factors, we hypothesized that the biological mechanism underlying their comorbidity might be explained, at least in part, by shared genetics. To assess their potential genetic relationship, we performed a two-sample mendelian randomization (2SMR) analysis on results from public genome-wide association studies (GWAS). This analysis confirmed previously reported genetic pleiotropy between endometriosis and endometrial cancer. We present robust evidence supporting a causal genetic association between endometriosis and ovarian cancer, particularly with the clear cell and endometrioid subtypes. Our study also identified genetic variants that could explain those associations, opening the door to further functional experiments. Overall, this work demonstrates the value of genomic analyses to support epidemiological data, and to identify targets of relevance in multiple disorders. 相似文献
96.
Alexandra Calle Víctor Toribio María Yez-M Miguel ngel Ramírez 《International journal of molecular sciences》2021,22(11)
Embryonic implantation is a key step in the establishment of pregnancy. In the present work, we have carried out an in-depth proteomic analysis of the secretome (extracellular vesicles and soluble proteins) of two bovine blastocysts embryonic trophectoderm primary cultures (BBT), confirming different epithelial–mesenchymal transition stages in these cells. BBT-secretomes contain early pregnancy-related proteins and angiogenic proteins both as cargo in EVs and the soluble fraction. We have demonstrated the functional transfer of protein-containing secretome between embryonic trophectoderm and maternal MSC in vitro using two BBT primary cultures eight endometrial MSC (eMSC) and five peripheral blood MSC (pbMSC) lines. We observed that eMSC and pbMSC chemotax to both the soluble fraction and EVs of the BBT secretome. In addition, in a complementary direction, we found that the pattern of expression of implantation proteins in BBT-EVs changes depending on: (i) their epithelial–mesenchymal phenotype; (ii) as a result of the uptake of eMSC- or pbMSC-EV previously stimulated or not with embryonic signals (IFN-τ); (iii) because of the stimulation with the endometrial cytokines present in the uterine fluid in the peri-implantation period. 相似文献
97.
Yangyang Xu Zhaofu Ding Haibin Zhu Yijun Zhang Stephan Knopf Pu Xiao Jacques Lalevée 《大分子材料与工程》2021,306(3):2000720
The introduction of metallic fillers to polymers via the photopolymerization approach can endow the composite materials with some unique properties, but the relevant research is still scarce due to the issue of light penetration and inner filter effect. Herein, for the first time the fabrication of photocomposites based on fine iron powder (i.e., a typical kind of metallic filler) is reported in this work. The free radical polymerization of two different acrylate monomers, poly(ethylene glycol) diacrylate and trimethylolpropane triacrylate, is performed in the presence of iron filler under mild conditions (i.e., light emitting diode (LED)@405 nm irradiation at room temperature under air). And the real-time Fourier transform infrared spectroscopy reveals remarkable photopolymerization kinetics of acrylates with high final conversions and fast polymerization rates despite the increasing contents of iron filler in the composites. Interestingly, the 3D printing technique is applied to the iron filler-based composites to produce tridimensional patterns with excellent spatial resolution. This work not only paves the way for the investigation of photocomposites based on metallic fillers through photochemical methods, but also broadens the potential application prospects. 相似文献
98.
The aim of this work is to propose an original solution to the acoustic impedance mismatch between a PZT transducer and a water load. The characteristic acoustic impedance of the PZT is around 33 MRayl. Theoretically, a quarter-wave layer with characteristic acoustic impedance equal to 7 MRayl is necessary to match the transducer to water. In practice, it is difficult to find a material with this particular impedance. Two or more quarter-wave layers may also be used. The following proposed solution consists in using two matching layers where one of them is the glue. Moreover, their thicknesses are not equal to a quarter of their individual wavelength. Once the glue is taken as the first matching layer, the specific material of the second layer can easily be found. In this work, the second layer, which is also the front layer, is made of glass. The thickness of each matching layer is then calculated as a function of the characteristic acoustic impedance of the two layers. The influence of the thickness of these layers is discussed. The proposed matching configuration is analyzed and theoretical results have been carefully and successfully compared with measurements. 相似文献
99.
A. Domingue K. Piyakis E. Sacher M. Di Renzo S. D nomm e T. H. Ellis 《The Journal of Adhesion》1993,40(2):151-162
The irreversibly bound interfacial layer deposited by the γ-aminopropysilanetriol adhesion promoter onto a crystalline silicon substrate, which remains even after profuse washing, was found by XPS to have resulted from the fragmentation and rearrangement of the original γ-aminopropylsilanetriol molecule. A mechanism is proposed, involving the homolytic scission of the terminal N-C bond. One of the subsequent reactions is believed to involve hydrogen loss by abstraction and the formation of a terminal vinyl group, which bonds to the substrate. Support for this mechanism is found in IR spectroscopy of this layer. 相似文献
100.
R. Gonzalez-Nunez B. D. Favis P. J. Carreau C. Lavalle 《Polymer Engineering and Science》1993,33(13):851-859
The morphology of the dispersed phase in immiscible polymer blends plays an important role in the determination of the final physical properties. This paper considers factors that influence the final state of deformation of the dispersed phase, and in particular, the formation of fibers and lamellae. Blends of polyethylene and nylon-6 were extruded by ribbon extrusion at different draw ratios. Prior to single-screw extrusion the materials were blended in a co-rotating twin-screw extruder, and the size of the dispersed phase was studied as a function of the viscosity ratio. As the blends are extruded into ribbons and drawn through the calender rolls, the morphology of the dispersed phase undergoes drastic transformations. The fiber formation is enhanced by increasing the draw ratio. At high draw ratios, long thin fibers are observed. Some biaxial deformation is obtained for the noncompatibilized systems when the extruded materials enter the calender with the maximum closing pressure applied to the rolls. The same effect is observed for the compatibilized systems with lower values of the viscosity ratio. As a general rule, it has been observed that the final dispersed phase deformation is diminished in interfacially compatibilized systems. 相似文献