Liquefied microcapsules as dual-Mmcrocarriers for 3D+3D bottom-up tissue engineering

Cell encapsulation systems must ensure the diffusion of molecules to avoid the formation of necrotic cores. The architectural design of hydrogels, the gold standard tissue engineering strategy, is thus limited to a microsize range. To overcome such a limitation, liquefied microcapsules encapsulating cells and microparticles are proposed. Microcapsules with controlled sizes with average diameters of 608.5 ± 122.3 µm are produced at high rates by electrohydrodynamic atomization, and arginyl-glycyl-aspartic acid (RGD) domains are introduced in the multilayered membrane. While cells and microparticles interact toward the production of confined microaggregates, on the outside cell-mediated macroaggregates are formed due to the aggregation of microcapsules. The concept of simultaneous aggregation is herein termed as 3D+3D bottom-up tissue engineering. Microcapsules are cultured alone (microcapsule1 ) or on top of 2D cell beds composed of human umbilical vein endothelial cells (HUVECs) alone (microcapsule2 ) or cocultured with fibroblasts (microcapsule3 ). Microcapsules are able to support cell encapsulation shown by LiveDead, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphofenyl)-2H-tetrazolium (MTS), and dsDNA assays. Only microcapsule3 are able to form macroaggregates, as shown by F-actin immunofluorescence. The bioactive 3D system also presented alkaline phosphatase activity, thus allowing osteogenic differentiation. Upon implantation using the chick chorioallontoic membrane (CAM) model, microcapsules recruit a similar number of vessels with alike geometric parameters in comparison with CAMs supplemented with basic fibroblast growth factor (bFGF).publishe

Minimalist tissue engineering approaches using low material-based bioengineered systems

From an “over-engineering” era in which biomaterials played a central role, now it is observed to the emergence of “developmental” tissue engineering (TE) strategies which rely on an integrative cell-material perspective that paves the way for cell self-organization. The current challenge is to engineer the microenvironment without hampering the spontaneous collective arrangement ability of cells, while simultaneously providing biochemical, geometrical, and biophysical cues that positively influence tissue healing. These efforts have resulted in the development of low-material based TE strategies focused on minimizing the amount of biomaterial provided to the living key players of the regenerative process. Through a “minimalist-engineering” approach, the main idea is to fine-tune the spatial balance occupied by the inanimate region of the regenerative niche toward maximum actuation of the key living components during the healing process.publishe

Tuneable spheroidal hydrogel particles for cell and drug encapsulation

The need to better mimic native tissues has accompanied research in tissue engineering and controlled drug delivery. The development of new platforms for cell and drug encapsulation followed the same trend, and studying the influence of the delivery material system's geometry has been gaining momentum. Aiming to investigate how an increase in surface area and varying particle shape could impact drug release and cell viability, a novel method was developed to produce spheroidal hydrogel particles with adjustable circularity, aiming to tune drug delivery. For this purpose, droplets of hydrogel precursor were squeezed between two superamphiphobic surfaces separated with spacers with different height, and then photo-crosslinked to maintain the acquired shape after de-sandwiching. Numerical modelling studies were performed to study the polymeric droplet geometry deformation process, which were consistent with experimentally obtained results. The spheroidal particles were produced under mild conditions using methacrylated chitosan, capable of encapsulating proteins or cells. Likely due to their higher surface area to volume-ratio, compared to spherical-shaped ones, spheroids presented an improved viability of encapsulated cells due to enhanced nutrient diffusion to the core, and led to a significantly faster drug release rate from the polymer network. These results were also assessed numerically, in which the drug release rate was computed for different spheroidal-like geometries. Hence, the described method can be used to manufacture spheroidal particles with tailored geometry that can be broadly applied in the biomedical field, including for drug delivery or as cell encapsulation platforms.I. M. Bjorge and A. M. S. Costa acknowledge financial support by the Portuguese Foundation for Science and Technology (FCT) with doctoral grants SFRH/BD/129224/2017 and SFRH/BD/101748/2014, respectively. This work was supported by the European Research Council grant agreement ERC-2014-ADG-669858 for the project "ATLAS". The work was developed within the scope of the project CICECO Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (FCT Ref. UID/CTM/50011/2013), and the project IPC/i3N Minho (FCT Ref. UID/CTM/50025/2013), financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement.info:eu-repo/semantics/publishedVersio

Body mass index, triglyceride-glucose index, and prostate cancer death : a mediation analysis in eight European cohorts

BACKGROUND: Insulin resistance is a hypothesised biological mechanism linking obesity with prostate cancer (PCa) death. Data in support of this hypothesis is limited. METHODS: We included 259,884 men from eight European cohorts, with 11,760 incident PCa's and 1784 PCa deaths during follow-up. We used the triglyceride-glucose (TyG) index as indicator of insulin resistance. We analysed PCa cases with follow-up from PCa diagnosis, and the full cohort with follow-up from the baseline cancer-free state, thus incorporating both PCa incidence and death. We calculated hazard ratios (HR) and the proportion of the total effect of body mass index (BMI) on PCa death mediated through TyG index. RESULTS: In the PCa-case-only analysis, baseline TyG index was positively associated with PCa death (HR per 1-standard deviation: 1.11, 95% confidence interval (CI); 1.01-1.22), and mediated a substantial proportion of the baseline BMI effect on PCa death (HRtotal effect per 5-kg/m2 BMI: 1.24; 1.14-1.35, of which 28%; 4%-52%, mediated). In contrast, in the full cohort, the TyG index was not associated with PCa death (HR: 1.03; 0.94-1.13), hence did not substantially mediate the effect of BMI on PCa death. CONCLUSIONS: Insulin resistance could be an important pathway through which obesity accelerates PCa progression to death

No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

Objective. Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods. Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results. We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 034, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions. rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers. (C) 2015 Elsevier Inc. All rights reserved.Peer reviewe

No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer.

ObjectiveClinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370.MethodsCentralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers).ResultsWe found no association with risk of ovarian cancer (OR=0.99, 95% CI 0.94-1.04, p=0.74) or breast cancer (OR=0.98, 95% CI 0.94-1.01, p=0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR=1.09, 95% CI 0.97-1.23, p=0.14, breast cancer HR=1.04, 95% CI 0.97-1.12, p=0.27; BRCA2, ovarian cancer HR=0.89, 95% CI 0.71-1.13, p=0.34, breast cancer HR=1.06, 95% CI 0.94-1.19, p=0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR=0.94, 95% CI 0.83-1.07, p=0.38), breast cancer (HR=0.96, 95% CI 0.87-1.06, p=0.38), and all other previously-reported associations.Conclusionsrs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers

The global, regional, and national burden of stomach cancer in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease study 2017

Etemadi A, Safiri S, Sepanlou SG, et al. The global, regional, and national burden of stomach cancer in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease study 2017. LANCET GASTROENTEROLOGY & HEPATOLOGY. 2020;5(1):42-54.Background Stomach cancer is a major health problem in many countries. Understanding the current burden of stomach cancer and the differential trends across various locations is essential for formulating effective preventive strategies. We report on the incidence, mortality, and disability-adjusted life-years (DALYs) due to stomach cancer in 195 countries and territories from 21 regions between 1990 and 2017. Methods Estimates from GBD 2017 were used to analyse the incidence, mortality, and DALYs due to stomach cancer at the global, regional, and national levels. The rates were standardised to the GBD world population and reported per 100 000 population as age-standardised incidence rates, age-standardised death rates, and age-standardised DALY rates. All estimates were generated with 95% uncertainty intervals (UIs). Findings In 2017, more than 1.22 million (95% UI 1.19-1.25) incident cases of stomach cancer occurred worldwide, and nearly 865 000 people (848 000-885 000) died of stomach cancer, contributing to 19.1 million (18.7-19.6) DALYs. The highest age-standardised incidence rates in 2017 were seen in the high-income Asia Pacific (29.5, 28.2-31.0 per 100 000 population) and east Asia (28.6, 27.3-30.0 per 100 000 population) regions, with nearly half of the global incident cases occurring in China. Compared with 1990, in 2017 more than 356 000 more incident cases of stomach cancer were estimated, leading to nearly 96 000 more deaths. Despite the increase in absolute numbers, the worldwide age-standardised rates of stomach cancer (incidence, deaths, and DALYs) have declined since 1990. The drop in the disease burden was associated with improved Socio-demographic Index. Globally, 38.2% (21.1-57.8) of the age-standardised DALYs were attributable to high-sodium diet in both sexes combined, and 24.5% (20.0-28.9) of the age-standardised DALYs were attributable to smoking in males. Interpretation Our findings provide insight into the changing burden of stomach cancer, which is useful in planning local strategies and monitoring their progress. To this end, specific local strategies should be tailored to each country's risk factor profile. Beyond the current decline in age-standardised incidence and death rates, a decrease in the absolute number of cases and deaths will be possible if the burden in east Asia, where currently almost half of the incident cases and deaths occur, is further reduced. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license