Differential lipid accumulation on HepG2 cells triggered by palmitic and linoleic fatty acids exposure

Lipid metabolism pathways such as β-oxidation, lipolysis and, lipogenesis, are mainly associated with normal liver function. However, steatosis is a growing pathology caused by the accumulation of lipids in hepatic cells due to increased lipogenesis, dysregulated lipid metabolism, and/or reduced lipolysis. Accordingly, this investigation hypothesizes a selective in vitro accumulation of palmitic and linoleic fatty acids on hepatocytes. After assessing the metabolic inhibition, apoptotic effect, and reactive oxygen species (ROS) generation by linoleic (LA) and palmitic (PA) fatty acids, HepG2 cells were exposed to different ratios of LA and PA to study the lipid accumulation using the lipophilic dye Oil Red O. Lipidomic studies were also carried out after lipid isolation. Results revealed that LA was highly accumulated and induced ROS production when compared to PA. Lipid profile modifications were observed after LA:PA 1:1 (v/v) exposure, which led to a four-fold increase in triglycerides (TGs) (mainly in linoleic acid-containing species), as well as a increase in cholesterol and polyunsaturated fatty acids (PUFA) content when compared to the control cells. The present work highlights the importance of balancing both PA and LA fatty acids concentrations in HepG2 cells to maintain normal levels of free fatty acids (FFAs), cholesterol, and TGs and to minimize some of the observed in vitro effects (i.e., apoptosis, ROS generation and lipid accumulation) caused by these fatty acids.info:eu-repo/semantics/publishedVersio

Phytosterols and novel triterpenes recovered from industrial fermentation coproducts exert in vitro anti‐inflammatory activity in macrophages

The unstoppable growth of human population that occurs in parallel with all manufacturing activities leads to a relentless increase in the demand for resources, cultivation land, and energy. In response, currently, there is significant interest in developing strategies to optimize any available resources and their biowaste. While solutions initially focused on recovering biomolecules with applications in food, energy, or materials, the feasibility of synthetic biology in this field has been demonstrated in recent years. For instance, it is possible to genetically modify Saccharomyces cerevisiae to produce terpenes for commercial applications (i.e., against malaria or as biodiesel). But the production process, similar to any industrial activity, generates biowastes containing promising biomolecules (from fermentation) that if recovered may have applications in different areas. To test this hypothesis, in the present study, the lipid composition of by‐products from the industrial production of β‐farnesene by genetically modified Saccharomyces cerevisiae are studied to identify potentially bioactive compounds, their recovery, and finally, their stability and in vitro bioactivity. The assayed biowaste showed the presence of triterpenes, phytosterols, and 1‐ octacosanol which were recovered through molecular distillation into a single fraction. During the assayed stability test, compositional modifications were observed, mainly for the phytosterols and 1‐octacosanol, probably due to oxidative reactions. However, such changes did not affect the in vitro bioactivity in macrophages, where it was found that the obtained fraction decreased the production of TNF‐α and IL‐6 in lipopolysaccharide (LPS)‐induced inflammation.info:eu-repo/semantics/publishedVersio

Mechanical joining methods for additive manufactured assembly tools

The use of additive manufacturing (AM) processes is growing in the manufacturing industry. One application with great potential for using these processes is the manufacture of assembly tools for a high-ly competitive markets, such as the automotive industry. A critical aspect of the assembly tool design is its capability to incorporate modifications even at a late stage of its development in very short time. In many cases, these modifications are achieved using metal inserts in the polymeric tool, which allow to add new geometric features. This capability increases the usefulness and versatility of components produced by AM and compensate for potential shortcomings of using additive mate-rials. The purpose of this paper is to evaluate the potential use of accessories in additive manufactured com-ponents. In addition, the effect of different percentages of infill tool material on the joining quality of accesso-ries is evaluated. This is done by performing a screw pull-out test on a ABS ESD-7 part, produced by fused deposition modelling. The following different joining solutions were compared and studied in this work: em-bedded inserts, glue, heating processes, pressure (Tap-in) and creation of threads, such as, printing the thread directly and machining the thread onto the material.Programa Operacional Competitividade e Internacionalização - COMPETE 2020, Projeto nº 002814, Ref. POCI-01-0247-FEDER-002814 entre a Univ. do Minho e a Bosc

A multicenter validation of an endoscopic classification with narrow band imaging for gastric precancerous and cancerous lesions

BACKGROUND AND STUDY AIM: The reliability and external validity of narrow band imaging (NBI) in the stomach have not been described consistently. The aim of the current study was to describe and estimate the accuracy and reliability of a simplified classification system for NBI in the diagnosis of gastric lesions. METHODS: Consecutive patients undergoing NBI endoscopy at two reference centers (n=85, 33% with dysplasia) were included in two studies. In total, 224 different areas were biopsied and recorded onto video. In the derivation study, previously described NBI features were analyzed in order to develop a simplified classification. In the validation study the accuracy and reliability of this classification were estimated among three groups of endoscopists with different levels of expertise in NBI. .RESULTS: The reliability/accuracy results from the derivation study allowed the creation of a simplified NBI classification. In the validation study, "regular vessels with circular mucosa" (pattern A) was associated with normal histology (accuracy 83%; 95% confidence interval [CI] 75?%-90%); "tubulo-villous mucosa" (pattern B) was associated with intestinal metaplasia (accuracy 84%; 95CI 77%-91%; positive likelihood ratio [LR+]=4.75); and "irregular vessels and mucosa" (pattern C) was associated with dysplasia (accuracy 95%; 95CI 90%-99%; LR+=44.33). The reproducibility of these patterns was high (k=0.62). "Light-blue crest" was moderately reliable (k=0.49) but specific (87%) for intestinal metaplasia. A variable vascular density (additional pattern+) was the best feature for Helicobacter pylori gastritis (accuracy 70%; 95CI 59%-80%) but showed only fair reliability (k=0.38). Non-experienced endoscopists presented lower agreement (k=0.6 vs. k=0.75) and accuracy (74% vs. 86%) than international experts/experienced endoscopists. CONCLUSION: A simplified NBI classification is accurate and reliable for the diagnosis of intestinal metaplasia and dysplasia. The classification should be further assessed and validated on a per-patient assessment of NBI, and by comparing NBI with other imaging technologies.This study was supported by a grant for medical investigation from the Portuguese Digestive Endoscopy Society (SPED 2009 Investigation Grant)

Presentation and validation of a new optical sensing concept based in a 3d-printing solution

In high competitive markets, such as the automotive industry, the better quality of products, reduction of manufacturing costs and the fulfilment of all delivery deadlines can only be achieved through continuous improvement of production capabilities. One current strategy is to develop and create smarter and adaptive assembly tools. Automation is a relevant area of development in the current industrial world and the baseline of the fourth industrial revolution (Industry 4.0). Namely, it is very important to use sensing components on jigs for assembly parts in the production line. The arrangement of sensing components on the assembly tools is very dependent of the product, making the project more complex and less flexible. This issue can penalise the productivity heavily, especially if a wide range of products and changeover operations are usual. The use of Additive Manufacturing (AM) is growing in the industry and offers a high potential for research and development in the present stage. The AM is advantageous in many areas, especially in the rapid construction of complex tools (RP). This paper presents a new optical sensing concept based on the 3D printing of internal circuits in the assembly tools. This solution can bring many advantages and increase tools flexibility.Programa Operacional de Competividade e Internacionalização - COMPETE 2020, Projeto nº 002814; Ref. POCI-01-0247-FEDER-002814, entre a Univ. Minho e a Bosc

The Usefulness of Inflammatory Biomarkers to Predict Anastomotic Leakage after Colorectal Surgery: Systematic Review and Meta-Analysis

Aim: Anastomotic leakage (AL) is a severe postoperative complication in colorectal surgery, but its preclinical diagnosis may improve outcomes and increase anastomotic salvage. This study aimed to assess the added value of serum biomarkers for early detection of colorectal AL. Method: We performed a comprehensive literature review, and a qualitative and quantitative analysis of papers retrieved from MEDLINE, Embase, PubMed, Web of Science, Scopus and the Cochrane Library. We included all studies published before September 2021 assessing the serum biomarkers white blood cells (WBC), C-reactive protein (CRP), procalcitonin (PCT) and calprotectin (CLP) for the early diagnosis of AL. Results: Fifteen studies that evaluated three different systemic biomarkers in the context of AL were identified, including 5150 patients. Diagnostic test accuracy was estimated for CRP and PCT. On postoperative day (POD) 5, the highest AUC (87.1%) and specificity (80.2%) values were estimated for CRP. Random-effects meta-analysis and total effect sizes estimation for the biomarkers CRP, PCT and WBC were performed according to POD. The concentration of serum biomarkers is significantly higher in patients presenting AL. Regarding the qualitative analysis, there was significant heterogeneity in the inclusion of different subcategories of the consensus definition of colorectal AL in each paper’s definition. Conclusion: The serum biomarkers CRP and PCT are moderate predictors for AL, showing a high heterogeneity among the studies. Combinations of these biomarkers might improve predictive accuracy, but more studies will be necessary to conduct a quality metaregression.info:eu-repo/semantics/publishedVersio

Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects

Introduction: A number of genetic-association studies have identified genes contributing to ankylosing spondylitis (AS) susceptibility but such approaches provide little information as to the gene activity changes occurring during the disease process. Transcriptional profiling generates a 'snapshot' of the sampled cells' activity and thus can provide insights into the molecular processes driving the disease process. We undertook a whole-genome microarray approach to identify candidate genes associated with AS and validated these gene-expression changes in a larger sample cohort

The role of climate, marine influence and sedimentation rates in late-Holocene estuarine evolution (SW Portugal)

Estuaries are sensitive to changes in global to regional sea level, to climate-driven variation in rainfall and to fluvial discharge. In this study, we use source and environmentally sensitive proxies together with radiocarbon dating to examine a 7-m-thick sedimentary record from the Sado estuary accumulated throughout the last 3.6 kyr. The lithofacies, geochemistry and diatom assemblages in the sediments accumulated between 3570 and 3240 cal. BP indicate a mixture between terrestrial and marine sources. The relative contribution of each source varied through time as sedimentation progressed in a low intertidal to high subtidal and low-energy accreting tidal flat. The sedimentation proceeded under a general pattern of drier and higher aridity conditions, punctuated by century-long changes of the rainfall regime that mirror an increase in storminess that affected SW Portugal and Europe. The sediment sequence contains evidence of two periods characterized by downstream displacement of the estuarine/freshwater transitional boundary, dated to 3570-3400 cal. BP and 3300-3240 cal. BP. These are intercalated by one episode where marine influence shifted upstream. All sedimentation episodes developed under high terrestrial sediment delivery to this transitional region, leading to exceptionally high sedimentation rates, independently of the relative expression of terrestrial/marine influences in sediment facies. Our data show that these disturbances are mainly climate-driven and related to variations in rainfall and only secondarily with regional sea-level oscillations. From 3240 cal. BP onwards, an abrupt change in sediment facies is noted, in which the silting estuarine bottom reaches mean sea level and continued accreting until present under prevailing freshwater conditions, the tidal flat changing to an alluvial plain. The environmental modification is accompanied by a pronounced change in sedimentation rate that decreased by two orders of magnitude, reflecting the loss of accommodation space rather than the influence of climate or regional sea-level drivers.FCT by Spanish Ministry of Science and Innovation [SFRH/BD/110270/2015, HAR2014-51830-P, HAR2011-29907-C03-00]FCTPortuguese Foundation for Science and Technology [PTDC/HISARQ/121592/2010]Instituto Dom Luiz-IDL [UID/GEO/50019/2013]info:eu-repo/semantics/publishedVersio

TRAF1/C5 but Not PTPRC Variants Are Potential Predictors of Rheumatoid Arthritis Response to Anti-Tumor Necrosis Factor Therapy

Background. The aim of our work was to replicate, in a Southern European population, the association reported in Northern populations between PTPRC locus and response to anti-tumor necrosis factor (anti-TNF) treatment in rheumatoid arthritis (RA). We also looked at associations between five RA risk alleles and treatment response. Methods. We evaluated associations between anti-TNF treatment responses assessed by DAS28 change and by EULAR response at six months in 383 Portuguese patients. Univariate and multivariate linear and logistic regression analyses were performed. In a second step to confirm our findings, we pooled our population with 265 Spanish patients. Results. No association was found between PTPRC rs10919563 allele and anti-TNF treatment response, neither in Portuguese modeling for several clinical variables nor in the overall population combining Portuguese and Spanish patients. The minor allele for RA susceptibility, rs3761847 SNP in TRAF1/C5 region, was associated with a poor response in linear and logistic univariate and multivariate regression analyses. No association was observed with the other allellic variants. Results were confirmed in the pooled analysis. Conclusion. This study did not replicate the association between PTPRC and the response to anti-TNF treatment in our Southern European population. We found that TRAF1/C5 risk RA variants potentially influence anti-TNF treatment response.This work was supported by a grant from Harvard-Portugal Program HMSP-ICS/SAU-ICT/0002/2010. Daniel H. Solomon received support for this work from the NIH (K24-AR-055989). Elizabeth W. Karlson received support for this work from NIH (K24-AR-AR0524). Reuma.pt received unrestricted grants from Abbott, Bristol-Myers Squibb, Merck Sharp and Dohme, Pfizer, Roche, and UCB Pharma