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71.
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
72.
Agata Wawrzkiewicz-Jaowiecka Anna Lalik Graa Soveral 《International journal of molecular sciences》2021,22(10)
The gonadal steroids, including androgens, estrogens and progestogens, are involved in the control of body fat distribution in humans. Nevertheless, not only the size and localization of the fat depots depend on the sex steroids levels, but they can also highly affect the functioning of adipose tissue. Namely, the gonadocorticoids can directly influence insulin signaling, lipid metabolism, fatty acid uptake and adipokine production. They may also alter energy balance and glucose homeostasis in adipocytes in an indirect way, e.g., by changing the expression level of aquaglyceroporins. This work presents the recent advances in understanding the molecular mechanism of how the gonadal steroids influence the functioning of adipose tissue leading to a set of detrimental metabolic consequences. Special attention is given here to highlighting the sexual dimorphism of adipocyte functioning in terms of health and disease. Particularly, we discuss the molecular background of metabolic disturbances occurring in consequence of hormonal imbalance which is characteristic of some common endocrinopathies such as the polycystic ovary syndrome. From this perspective, we highlight the potential drug targets and the active substances which can be used in personalized sex-specific management of metabolic diseases, in accord with the patient’s hormonal status. 相似文献
73.
Tomasz Z. Tomkiewicz Nuria Surez-Herrera Frans P. M. Cremers Rob W. J. Collin Alejandro Garanto 《International journal of molecular sciences》2021,22(9)
The discovery of novel intronic variants in the ABCA4 locus has contributed significantly to solving the missing heritability in Stargardt disease (STGD1). The increasing number of variants affecting pre-mRNA splicing makes ABCA4 a suitable candidate for antisense oligonucleotide (AON)-based splicing modulation therapies. In this study, AON-based splicing modulation was assessed for 15 recently described intronic variants (three near-exon and 12 deep-intronic variants). In total, 26 AONs were designed and tested in vitro using a midigene-based splice system. Overall, partial or complete splicing correction was observed for two variants causing exon elongation and all variants causing pseudoexon inclusion. Together, our results confirm the high potential of AONs for the development of future RNA therapies to correct splicing defects causing STGD1. 相似文献
74.
Olga Shilova Elena Shramova Galina Proshkina Sergey Deyev 《International journal of molecular sciences》2021,22(9)
Cancer cells frequently overexpress specific surface receptors providing tumor growth and survival which can be used for precise therapy. Targeting cancer cell receptors with protein toxins is an attractive approach widely used in contemporary experimental oncology and preclinical studies. Methods of targeted delivery of toxins to cancer cells, different drug carriers based on nanosized materials (liposomes, nanoparticles, polymers), the most promising designed light-activated toxins, as well as mechanisms of the cytotoxic action of the main natural toxins used in modern experimental oncology, are discussed in this review. The prospects of the combined therapy of tumors based on multimodal nanostructures are also discussed. 相似文献
75.
Dorota Butkiewicz Magorzata Krzeniak Agnieszka Gdowicz-Kosok Monika Giglok Magorzata Marszaek-Zeczak Rafa Suwiski 《International journal of molecular sciences》2021,22(11)
For non-small cell lung cancer (NSCLC), radiotherapy (RT) and platinum-based chemotherapy (CHT) are among the main treatment options. On the other hand, radioresistance and cytotoxic drug resistance are common causes of failure. The epidermal growth factor receptor (EGFR) plays an important role in radioresponse and therapy resistance. We hypothesized that single nucleotide polymorphisms (SNPs) in the EGFR gene might affect individual sensitivity to these treatments, and thus, therapy outcome and prognosis. The association between functional EGFR SNPs and overall (OS), locoregional recurrence-free (LFRS), and metastasis-free (MFS) survival was examined in 436 patients with unresectable NSCLC receiving RT and platinum-based CHTRT. In a multivariate analysis, the rs712830 CC homozygotes showed reduced OS in the whole group (p = 0.039) and in the curative treatment subset (p = 0.047). The rs712829 TT genotype was strongly associated with decreased LRFS (p = 0.006), and the T-C haplotype was a risk factor for locoregional recurrence in our patients (p = 0.003). The rs2227983 GG alone and in combination with rs712829 T was an indicator of unfavorable LRFS (p = 0.028 and 0.002, respectively). Moreover, significant independent effects of these SNPs on OS, LRFS, and MFS were observed. Our results demonstrate that inherited EGFR gene variants may predict clinical outcomes in NSCLC treated with DNA damage-inducing therapy. 相似文献
76.
Mina Zare Ashkan Bigham Mohamad Zare Hongrong Luo Erfan Rezvani Ghomi Seeram Ramakrishna 《International journal of molecular sciences》2021,22(12)
Poly(2-hydroxyethyl methacrylate) (pHEMA) as a biomaterial with excellent biocompatibility and cytocompatibility elicits a minimal immunological response from host tissue making it desirable for different biomedical applications. This article seeks to provide an in-depth overview of the properties and biomedical applications of pHEMA for bone tissue regeneration, wound healing, cancer therapy (stimuli and non-stimuli responsive systems), and ophthalmic applications (contact lenses and ocular drug delivery). As this polymer has been widely applied in ophthalmic applications, a specific consideration has been devoted to this field. Pure pHEMA does not possess antimicrobial properties and the site where the biomedical device is employed may be susceptible to microbial infections. Therefore, antimicrobial strategies such as the use of silver nanoparticles, antibiotics, and antimicrobial agents can be utilized to protect against infections. Therefore, the antimicrobial strategies besides the drug delivery applications of pHEMA were covered. With continuous research and advancement in science and technology, the outlook of pHEMA is promising as it will most certainly be utilized in more biomedical applications in the near future. The aim of this review was to bring together state-of-the-art research on pHEMA and their applications. 相似文献
77.
《International Journal of Industrial Ergonomics》2014,44(5):747-752
The purpose of this study is to validate an analytical method in assessing demanded mental workloads for physical therapists, and to discuss its possible ergonomics implications on the design of healthcare working systems in which physical therapists are considered as the users. A task analysis was first used to understand the operation steps of three identified physical therapies. Then, the McCracken–Aldrich technique was applied to assign ratings of mental workload demanded for performing each step of the therapies. Finally, the assigned ratings were validated by the analysis of correlation with the answers of the NASA-TLX questionnaire collected from seventeen physical therapists in the rehabilitation center of a university-affiliated hospital. Results showed that the proposed McCracken–Aldrich technique was suitable as an analysis tool for predicting metal workloads of physical therapists. Some possible implications about the information provision and user interface design for reducing therapists' mental workloads on current therapy operations were discussed.Relevance to industryResults of this paper are expected to contribute the research and development in healthcare industry on its system design and workflow analysis. 相似文献
78.
Cameron Allan Gunn Jennifer L. DicksonChristopher G. Pretty Jane M. AlsweilerAdrienne Lynn Geoffrey M. ShawJ. Geoffrey Chase 《Computer methods and programs in biomedicine》2014
Introduction
Hyperglycaemia is a common complication of stress and prematurity in extremely low-birth-weight infants. Model-based insulin therapy protocols have the ability to safely improve glycaemic control for this group. Estimating non-insulin-mediated brain glucose uptake by the central nervous system in these models is typically done using population-based body weight models, which may not be ideal.Method
A head circumference-based model that separately treats small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) infants is compared to a body weight model in a retrospective analysis of 48 patients with a median birth weight of 750 g and median gestational age of 25 weeks. Estimated brain mass, model-based insulin sensitivity (SI) profiles, and projected glycaemic control outcomes are investigated. SGA infants (5) are also analyzed as a separate cohort.Results
Across the entire cohort, estimated brain mass deviated by a median 10% between models, with a per-patient median difference in SI of 3.5%. For the SGA group, brain mass deviation was 42%, and per-patient SI deviation 13.7%. In virtual trials, 87–93% of recommended insulin rates were equal or slightly reduced (Δ < 0.16 mU/h) under the head circumference method, while glycaemic control outcomes showed little change.Conclusion
The results suggest that body weight methods are not as accurate as head circumference methods. Head circumference-based estimates may offer improved modelling accuracy and a small reduction in insulin administration, particularly for SGA infants. 相似文献79.
Richard V. Flor Le Tiet Hecking Brian David Martin 《Journal of the American Oil Chemists' Society》1993,70(2):199-203
Criteria for authentic olive oils were developed from isocratic high-performance liquid chromatography analyses of 99 olive
oils from the major Mediterranean producers in the 1983–1986 crop years. Authentic olive oils include extra virgin, virgin
and pure or refined oils, but exclude all reesterified and adulterated oils. The extra virgin through pure grades will have
a combined area for the LOO (C18:2C18:1C18:1), LOP (C18:2C18:1C16:0), OOO (C18:1C18:1C18:1), POO (C16:0C18:1C18:1), POP (C16:0C18:1C18:1), and SOO (C18:0C18:1C18:1) peaks between 82.0 and 92.6% of the total area (L, linoleic; O, oleic; P, palmitic; S, stearic). Authentic oils will have
ratios of LOO/LOP and OOO/POO that coincide with a line defined by OOO/POO=0.7844(LOO/LOP)+0.0968; correlation coefficient
is 0.885. Authentic oils will not have a trilinolein (LLL) peak over 0.5% in area. Neither triolein (OOO) nor any other single
peak suffices to characterize an olive oil sample as one of the authentic grades. 相似文献
80.
包边技术是提高大尺寸激光玻璃饱和增益系数的关键技术.采用传统的方法熔制玻璃,研究了P2O5含量对P2O5-Al2O3-B2O3-CuCl-Na2O-ZnO磷酸盐包边玻璃的折射率、热膨胀系数、玻璃转变温度、膨胀软化温度以及化学稳定性的影响.结果表明:当P2O5的摩尔分数为60%左右,玻璃样品具有最高的折射率(1.5220)、最低的玻璃转变温度(352.4℃)、较好的化学稳定性[0.52mg/(cm2·d)]和适宜的热膨胀系数(128.427×10-7/℃),是用作钕磷酸盐激光玻璃硬包边的理想材料. 相似文献