Orientador: Rejane Maira Góes / Resumo: O câncer de próstata (CaP) é um dos tipos mais recorrentes de câncer em homens e o consumo excessivo de lipídeos saturados favorece o seu desenvolvimento. Ao contrário, dietas ricas em ácidos graxos poli-insaturados (PUFA) tipo ômega-3 (n-3) tem sido associadas com menor incidência do CaP. O presente trabalho avaliou as repercussões do consumo de ácidos graxos PUFAs n-3 da série marinha, ácido docosahexaenoico (DHA) e ácido eicosapentaenoico (EPA), sobre a progressão tumoral na próstata ventral de camundongos transgênicos para o adenocarcinoma de próstata (TRAMP). Camundongos TRAMP foram alimentados com dieta padrão e eutanasiados com 8 (C8), 12 (C12) e 20 (C20) semanas de vida ou então alimentados com uma dieta rica em óleo de peixe (10% óleo de peixe) a partir da oitava semana de vida e então eutanasiados com 12 (T12) ou 20 semanas (T20). Os resultados adquiridos demonstraram o aumento na proliferação celular bem como na expressão tecidual do receptor de andrógeno (AR) e glicocorticoide (GR) e no número de linfócitos T na próstata dos grupos controles conforme o aumento da idade e da agressividade das lesões. A intervenção dietética com PUFAs n-3 proporcionou a preservação do microambiente glandular levando a uma menor frequência de lesões proliferativas, indicando um atraso na progressão tumoral, onde foi observado níveis de proliferação celular, da expressão tecidual de AR e GR e de linfócitos T inferiores que seus controles de mesma idade. Ainda, o consumo de DHA/EPA pro... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Prostate cancer (PCa) is one of the most frequent cancers among male individual and saturated lipid intake is linked to its development. However, diets rich in omega-3 (n-3) polyunsaturated fatty acid (PUFA) have been associated to lower PCa development risk. The present study assessed the outcome of the marine n-3 PUFA intake, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), upon tumor progression at the transgenic adenocarcinoma of the mouse prostate (TRAMP). TRAMP mice were chow-fed and euthanized at 8 (C8), 12 (C12) and 20th (C20) week of age or fed with a fish oil-enriched diet from 8 to 12 (T12) or 20th (T20) week of age and then euthanized. The results indicated an increase in proliferation rate, tissue expression of androgen receptor (AR) and glucocorticoid receptor (GR) and the number of T-cells at the prostate of the control groups according to the increase of age and aggressiveness of the lesions. Dietary intervention with n-3 PUFA led to the maintenance of the glandular microenvironment, highlighted by a reduction of the frequency of proliferative lesions, indicating a delay in PCa progression whereas the levels of cell proliferation, tissue expression of AR and GR and the number of T-cells were lower than the control groups of the same age. Also, DHA/EPA intake promoted a lowering effect of serum triglycerides and cholesterol, improving the metabolic profile of these animals. Thereby incorporation o DHA/EPA on diet is capable of decrease the severity o... (Complete abstract click electronic access below) / Mestre

Syfte. Syftet med denna litteraturstudie var att undersöka om orala tillskott av omega-3 har någon effekt på torra ögon. Metod. Den här litteraturstudien baserades på fem utvalda artiklar som söktes fram via sökmotorn Pubmed den 28 mars. Sökorden var “omega 3 supplement AND dry eye”. Olika begränsningar gjordes såsom tidsgräns för utgivning: mellan år 2015 till 2022 och Peer-reviewed randomiserad kontrollerade studier. Artiklar som inte gick i linje med den här litteraturstudiens syfte valdes bort, kvar fanns fyra artiklar. Den sista utvalda artikeln var en av tre ”given som förslag på citatmatchning” av sökmotorn Pubmed, vid angiven sökning ovan. Resultat. Av de fem artiklarna kunde två artiklar stödja en främjande effekt av omega-3 på dry eye disease (DED) och en artikel visade en statistisk signifikant positiv effekt på symtom i OSDI poäng i en subgrupp med svåra DED-symtom ≥ 52. Två av artiklarna kunde inte som slutsats stödja en positiv effekt av omega-3 på DED trots positiva effekter på korneal infärgning, Schirmer´s test, konjunktival infärgning samt TBUT, så var de inte statistiskt signifikanta, jämfört med placebogruppen. I de två artiklarna där en främjande effekt av omega-3 sågs på DED kunde det ses en positiv statistisk signifikant effekt på Ocular Surface Disease Index (OSDI) poäng, tårosmolaritet, TBUT med mera. Mängden deltagare varierade mellan studierna, även ålder, region, sammansättningen på fettsyrorna och biotillgängligheten av supplementen varierade, vilket kan ha påverkat studiernas resultat.Slutsats. Effekten av omega-3 på DED varierade mellan studierna. Själva sammansättningen på fettsyrorna påverkade resultaten där ökad biotillgänglighet hos omega-3, i återförestrad form och i form av krillolja (triglyceridform) visades ha en större effekt än omega-3 i etylesterform vid DED. Även addition av GLA till omega-3 supplementen hade en positiv effekt på symtom hos personer med svåra DED symtom. Fler studier behövs för en fullständig förståelse vad gäller dos och form av omega-3 samt för att utreda vilken svårighetsgrad av DED som kan dra nytta av omega-3-behandling. Framtida studier behöver även undersöka huruvida individanpassad terapi med Omega-3 kan användas vid DED. / Purpose. This literature study aimed to investigate whether oral omega-3 supplements affect dry eyes. Method. This literature review was based on five selected articles from the search engine Pubmed on 28 March. The keywords were "omega 3 supplement AND dry eye". There was inclusion criteria such as articles published between the years 2015 and 2022 and the articles needed to be Peer-reviewed randomized controlled trials. Articles in line with the purpose of this literature study were selected, and the outcome was four articles. The last article selected was one out of three included in the “suggestions for citation matching” by Pubmed, using the above-mentioned criteria. Results. Of the five articles, two articles could support a promoting effect of omega-3 on DED. One article showed a statistically significant positive impact on symptoms in OSDI scores in a subgroup with severe symptoms ≥ 52. In the two articles that could support a promoting effect of omega-3 on DED, a positive, statistically significant impact could be seen on OSDI scores, tear osmolarity, TBUT, and more. Two of the articles could not support a positive effect of omega-3 on DED. Even though there were positive effects on corneal staining, Schirmer´s test, conjunctival staining, and TBUT, they were not statistically significant compared with the placebo group. However, the number of participants varied between studies, which also varied for age, region, the composition of the fatty acids, and bioavailability of the supplement.Conclusion. The effect of omega-3 on DED varies between studies. The actual composition of the fatty acids seems to impact the result where increased bioavailability of omega-3, which is in re-esterified form, and krill oil that is in triglyceride form has a more significant effect than omega-3 in ethyl ester form. The addition of GLA to the omega-3 supplement also positively impacted symptoms in people with severe symptoms. More studies are needed to thoroughly understand the dose and form of omega-3, and severity of DED. But studies are also required to learn about individualized therapy, and if it can be applicable using omega-3 on DED.

Indiana University-Purdue University Indianapolis (IUPUI) / Omega-3 polyunsaturated fatty acids (n-3 PUFAs) relieve the symptoms of a wide variety of chronic inflammatory disorders. Typically, they must be obtained in the diet from sources such as fish oils. Docosahexaenoic acid (DHA) is one of these n-3 PUFAs. As yet the structural mechanism responsible for the health benefits within the body is not completely understood. One model that has emerged from biochemical and imaging studies of cells suggests that n-3 PUFAs are taken up into phospholipids in the plasma membrane. Thus the focus here is on the plasma membrane as a site of potential structural modification by DHA. Within cellular membranes, the huge variety of molecules (called lipids) which constitute the membrane suggest inhomogeneous mixing, thus domain formation. One potential domain of interest is called the lipid raft, which is primarily composed of sphingomyelin (SM) and cholesterol (chol). Here the molecular organization of [2H31]-N-palmitoylsphingomyelin (PSM-d31) mixed with 1-palmitoyl-2-docosahexaenoylphosphatylcholine (PDPC) or 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), as a monounsaturated control, and cholesterol (chol) (1:1:1 mol) in a model membrane was examined by solid state 2H NMR spectroscopy. Solid state 2H NMR spectroscopy extracts details of molecular orientation and anisotropy of molecular reorientation by analysis of the lineshape. This essentially non-invasive technique allows for a direct measurement of dynamics in bulk materials which has been extensively applied to biological materials. It is a niche area of NMR for which standard software often lack necessary features. Two software programs, “EchoNMR processor” and “EchoNMR simulator”, collectively known as “EchoNMR tools”, that were developed to quickly process and analyze one-dimensional solid-state NMR data, will be described along with some theoretical background of the techniques used. EchoNMR tools has been designed with a focus on usability and the open-source mindset. This is achieved in the in the MATLAB® programming environment which allows for the development of the graphical user interfaces and runs as an interpreter which allows the code to be open-source. The research described here on model membranes demonstrates the utility of the software. The NMR spectra for PSM-d31 in mixtures with PDPC or POPC with cholesterol were interpreted in terms of the presence of nano-sized SM-rich/chol-rich (raft-like) and PC-rich/chol-poor (non-raft) domains that become larger when POPC was replaced by PDPC. An increase in the differential in order and/or thickness between the two types of domains is responsible. The observation of separate signals from PSM-d31, and correspondingly from [3α-2H1]cholesterol (chol-d1) and 1-[2H31]palmitoyl-2-docosahexaenoylphosphatidylcholine (PDPC-d31), attributed to the raft-like and non-raft domains enabled the determination of the composition of the domains. Most of the SM (84%) and cholesterol (88%) was found in the raft-like domain. There was also a substantial amount of PDPC (70%) in the raft-like domain that appears to have minimal effect on the order of SM. PDPC molecules sequestering into small groups to minimize the contact of DHA chains with cholesterol is one possible explanation that would also have implications on raft continuity. These results refine the understanding of how DHA may modulate the structure of raft domains in membranes.

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Micro-scale processing (MSP) techniques are miniaturized version of upstream and downstream conventional unit operations that are designed to accelerate the pace of bioprocess design and development. Previous ‘dead end’ filtration studies have demonstrated the usefulness of this concept for membrane filtration processes. However, these experiments were performed without stirring which is the most common strategy to control the effects of concentration polarization and fouling on filtration performance. In this work, the pressure-driven stirred conditions of a conventional stirred-cell module were integrated with a 96-well filter plate to develop a high throughput technique called ‘stirred-well filtration’ (SWF). The design allowed for up to eight constant flux filtration experiments to be conducted at once using a multi-rack programmable syringe pump and a magnetic lateral tumble stirrer. An array of pressure transducers was used to monitor the transmembrane pressure (TMP) in each well. The protein sieving behavior and fouling propensity of Omega™ ultrafiltration membranes were assessed via a combination of hydraulic permeability measurements and protein sieving tests in constant filtrate flux mode. The TMP profile during filtration of bovine serum albumin (BSA) solution was strongly dependent on the stirring conditions – for example the maximum TMP in the stirred wells were an average of 7.5, 3.8, and 2.6 times lower than those in the unstirred wells at filtrate fluxes of 12, 36, and 60 LMH (5, 15, and 25 μL/min) respectively. The consistency of the data across different wells for the same stirring condition was very good. To demonstrate the effectiveness of the SWF technique, the eight tests for a simple 2^2 factorial design-of-experiments (DOE) test with duplicates was run to evaluate the effect of solution pH and salt concentration on protein filtration. The combination of SWF with statistical methods such as DOE is shown to be an effective strategy for high-throughput optimization of membrane filtration processes. / Dissertation / Master of Applied Science (MASc)

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