As growth of the elderly population continues to increase alongside improvements in percutaneous and minimally invasive interventions, cardiac surgeons question the role of high‐risk surgery in ...treating these patients. TAVR has transformed the management of symptomatic severe aortic stenosis in elderly patients and has become standard therapy for patients greater than 80 years of age. With improvements in procedural risks and technical complications for both transcatheter valves and percutaneous interventions, should we rethink the operative strategies for octogenarians and nonagenarians, particularly as they apply to concurrent high‐risk operations?
For over three decades, Chinese hamster ovary (CHO) cells have been the chosen expression platform for the production of therapeutic proteins with complex post‐translational modifications. However, ...the metabolism of these cells is far from perfect and optimized, and requires substantial know how and process optimization and monitoring to perform efficiently. One of the main reasons for this is the production and accumulation of toxic and growth‐inhibiting metabolites during culture. Lactate and ammonium are the most known, but many more have been identified. In this review, an overview of metabolites that deplete and accumulate throughout the course of cultivations with toxic and growth inhibitory effects to the cells is presented. Further, an overview of the CHO metabolism with emphasis to metabolic pathways of amino acids, glutathione (GSH), and related compounds which have growth‐inhibiting and/or toxic effect on the cells is provided. Additionally, relevant publications which describe the applications of metabolomics as a powerful tool for revealing which reactions occur in the cell under certain conditions are surveyed and growth‐inhibiting and toxic metabolites are identified. Also, a number of resources that describe the cellular mechanisms of CHO and are available on‐line are presented. Finally, the application of this knowledge for bioprocess and medium development and cell line engineering is discussed.
Chinese hamster ovary (CHO) cells are the chosen expression platform for the production of therapeutic proteins. ‘Omics data sets can aid and guide the rational design and generation of mammalian cells factories free of unwanted metabolic products and therefore capable of achieving higher cell densities and productivities. In this review, a number of metabolites depleting and accumulating throughout the course of cultivations, that have toxic and growth inhibitory effects to the cells are presented. Additionally, the potential application of this knowledge along with the use of analytical methods and on‐line metabolic resources for enhancing CHO cell lines by combining media development and cell line engineering approaches is discussed.
The present work describes the engineering of anti-PSMA peptide-decorated exosome mimetics (EMs) targeting advanced prostate cancer (PC). The targeted EMs were produced from anti-PSMA peptide, ...WQPDTAHHWATL, expressing U937 monoblastic cells, followed by successive extrusion cycles. The engineered EMs were nanosized, produced at a high yield, and displayed the anti-PSMA peptide, exosomal markers and monocytes proteins on their surface. As anticipated, PSMA-EMs showed increased cellular internalization in PSMA positive PC cell lines (LNCaP and C4-2B), compared to unmodified EMs. Most importantly, higher tumour targeting was observed in solid C4-2B tumours, following intravenous administration, confirming their targeting ability in vivo. Overall, our study indicates that the engineered anti-PSMA peptide-targeted EMs can be a promising drug delivery system for advanced PC.
Monoblastic U937 cells were transfected by nucleofection to express the PSMA targeting peptide on their membrane surface. The cells were extruded to produce the PSMA-targeted exosome mimetics with active targeting properties and improved internalization in PSMA expressing tumour in vitro and in vivo. Display omitted
Doxorubicin (DOX)-loaded lysolipid temperature-sensitive liposomes (LTSLs) are a promising stimuli-responsive drug delivery system that rapidly releases DOX in response to mild hyperthermia (HT). ...This study investigates the influence of loaded DOX crystals on the thermosensitivity of LTSLs and their therapeutic efficacy in vitro and in vivo. The properties of DOX crystals were manipulated using different remote loading methods (namely (NH4)2SO4, NH4-EDTA and MnSO4) and varying the lipid:DOX weight ratio during the loading step. Our results demonstrated that (NH4)2SO4 or NH4-EDTA remote loading methods had a comparable encapsulation efficiency (EE%) into LTSLs in contrast to the low DOX EE% obtained using the metal complexation method. Cryogenic transmission electron microscopy (cryo-TEM) revealed key differences in the nature of DOX crystals formed inside LTSLs based on the loading buffer or/and the lipid:DOX ratio used, resulting in different DOX release profiles in response to mild HT. The in vitro assessment of DOX release/uptake in CT26 and PC-3 cells revealed that the use of a high lipid:DOX ratio exhibited a fast and controlled release profile in combination with mild HT, which correlated well with their cytotoxicity studies. Similarly, in vivo DOX release, tumour growth inhibition and mice survival rates were influenced by the physicochemical properties of LTSLs payload. This study demonstrates, for the first time, that the characteristics of DOX crystals loaded into LTSLs, and their conformational rearrangement during HT, are important factors that impact the TSLs performance in vivo.
The nature of doxorubicin crystals influences its release from low temperature-sensitive liposomes in response to mild hyperthermia. Display omitted
Tissue tropism in parasitic diseases Silva Pereira, Sara; Trindade, Sandra; De Niz, Mariana ...
Open biology,
05/2019, Letnik:
9, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Parasitic diseases, such as sleeping sickness, Chagas disease and malaria, remain a major cause of morbidity and mortality worldwide, but particularly in tropical, developing countries. Controlling ...these diseases requires a better understanding of host-parasite interactions, including a deep appreciation of parasite distribution in the host. The preferred accumulation of parasites in some tissues of the host has been known for many years, but recent technical advances have allowed a more systematic analysis and quantifications of such tissue tropisms. The functional consequences of tissue tropism remain poorly studied, although it has been associated with important aspects of disease, including transmission enhancement, treatment failure, relapse and clinical outcome. Here, we discuss current knowledge of tissue tropism in Trypanosoma infections in mammals, describe potential mechanisms of tissue entry, comparatively discuss relevant findings from other parasitology fields where tissue tropism has been extensively investigated, and reflect on new questions raised by recent discoveries and their potential impact on clinical treatment and disease control strategies.
Broad variations in dietary and physical activity patterns are part of nutritional transition concept. An additional nutritional transition has as main characteristic the change of consumption of ...processed foods for ultra-processed foods (UPF). This study aims to evaluate trends of UPF availability in Portuguese population and its association with diet-related non-communicable diseases (NCD) health indicators. This ecological study used data from the Household Budget Surveys conducted by the National Statistics Institute each 5 years within a national representative sample of households. The percentage of UPF was calculated based on the total daily amount of food and beverages available per capita (in grams). Data from the years 1990, 1995, 2000 and 2005 were used, which were retrieved from DAFNE-Anemos Software. NCD age-standardised mortality, prevalence and incidence were obtained from the Global Burden of Disease database, for the years 2000, 2005, 2010 and 2015. Between 1990 and 2005, the UPF availability increased from 3·9 % to 13·8 %. Over the years, almost all food and beverages categories increased the UPF availability contribution, mainly noticeable for milk, sugar, cereal and meat products. Positive correlations were observed between UPF availability and digestive diseases both in prevalence (r = 0·062; P = 0·037) and incidence (r = 0·005; P = 0·010) measures. Neoplasms incidence also showed positive correlation with UPF availability (r = 0·002; P = 0·012). Trends in UPF availability in Portugal increased exponentially. At the same time, there is a trend towards a decrease in unprocessed and processed food availability. The Portuguese population should be made aware of the health risks resulting from excessive consumption of UPF.
•First report of cyanobacterial EPS/PVA nanofibres produced by electrospinning.•Nanofibres show smooth morphology, no beads and diameter between 54 and 133nm.•Mechanical analyses confirm miscibility ...and tanδ decrease between 10 and 30°C.•PVA/EPS membrane shows the best thermo-mechanical properties between 10 and 50°C.•Membranes resist more against disintegration and increase 5% Cr binding capacity.
A series of polyvinyl alcohol (PVA), PVA/chitosan (CS) and PVA/cyanobacterial extracellular polymeric substances (EPS) blended nanofibrous membranes were produced by electrospinning using a microfiltration poly(vinylidene fluoride) (PVDF) basal membrane, for potential applications in water filtration. Nanofibres were obtained from solutions of 20% (w/w) PVA with 1% (w/w) CS or EPS, using a weight ratio of 60/40. Blended nanofibres have shown a smooth morphology, no beads formation and diameters between 50 and 130nm. Thermo-mechanical analysis demonstrated that there were inter and/or intramolecular hydrogen bonds between the molecules of PVA/CS and PVA/EPS in the blends. The electrospun blended PVA/EPS membrane showed better tensile mechanical properties when compared with PVA and PVA/CS, and resisted more against disintegration in the temperature range between 10 and 50°C. Finally, the blended membranes have shown an increase in chromium binding capacity of 5%. This is the first successful report of a blended membrane of electrospinned cyanobacterial polysaccharide with PVA.
The dissonance between what teenagers learn in classrooms and their everyday lives is not a recent phenomenon, but it is increasingly relevant as school systems are unable to follow the evolution of ...media and society beyond traditional concerns regarding the protection of young people. An overly scholarly view of learning continues to prevail in our society, which seems to marginalize the knowledge that young people develop with and through media and digital platforms. Based on questionnaires, workshops, and interviews conducted with Portuguese teenagers, aged 12 to 16 years old (N=78), attending an urban and a rural school in the North of the country, this paper aims to understand how these teens are learning to use the media, what motivates them, and if their media practices contribute to the acquisition of skills and competencies useful to their lives inside and outside school. The research main results confirm the existence of a gap between formal and informal education. Informal education is mainly motivated by their needs and peer influence. Colleagues and family, alongside the Internet and self-discovery, appear as important sources of knowledge. Another important conclusion is that informal learning strategies contribute to the development of skills and competencies that are useful from a school viewpoint.
Enzymes’ machinery has been an inspiration for chemists. Peptides are vital players in the origin of life, being ancestors of complex enzymes. Even short peptides that are simple in terms of the ...number of residues are reprogrammable and built to encode chemical information for catalysis, substrate recognition, and molecular interactions. The combinatorial search of the sequence space led to identifying peptides with catalytic activities. However, most of these sequences remain unevolved, leading to modest rates in aqueous media. Short peptides present conformational flexibility, which is their primary liability for catalysis. To overcome this, supramolecular motifs and secondary frameworks are used as scaffolds to incorporate catalytic residues and improve their efficiency. This review discusses the strategies used to discover and evolve catalytic function in short peptides beyond the de novo design and the advantages of using these approaches to enhance catalysis.
PDF
